Research activity information

• Nov. 2017 Japanese Environmental Mutagen Society, Oxford Journal Award


• Sep. 2017 Fanconi Anemia Research Fund, Travel Award, Fatty aldehyde dehydrogenase as a novel binding partner of FANCD2

• Dynamics of Fanconi anemia protein D2 in association with nuclear lipid droplet formation

  Tomoya Hotani, Motonari Goto, Yukie Otsuki, Shun Matsuda, Nobuhiro Wada, Masakazu Shinohara, Tomonari Matsuda, Masayuki Yokoi, Kaoru Sugasawa, Yuki Ohsaki, Wataru Sakai

  Summary Fanconi anemia (FA) is a rare genetic disease caused by the loss of function of one of the 22 associated genes and is characterized by bone marrow failure, cancer predisposition, and developmental defects. The proteins encoded by these genes (FA proteins) mainly function in DNA damage response and repair. Although FA deficiency has multiple effects on the regulation of lipid metabolism, the molecular function of FA proteins in the context of FA pathology remains unclear. In the present study, we demonstrated that FANCD2, a key component of FA proteins, interacts with lipid metabolism-related factors and that FANCD2 deficiency downregulates the cellular levels of fatty acids. Moreover, a portion of FANCD2 is localized to nuclear lipid droplets in response to oleic acid treatment. These subcellular dynamics are independent of FANCD2 monoubiquitination, which is essential for the DNA damage response. Collectively, these findings demonstrate that FANCD2 responds to not only DNA damage but also oleic acid exposure, providing insights into the pathogenesis of lipid dysregulation in FA.

  Cold Spring Harbor Laboratory, Feb. 2025


• Identification of novel mutations and reassignment of archival xeroderma pigmentosum group C cell strains from Japanese patients.

  Hirotaka Kobayashi, Franklin Mayca Pozo, Wataru Sakai, Kenji Sato, Kaoru Sugasawa

  Nov. 2022, The Journal of dermatology, 50(3) (3), 407 - 408, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Histone deacetylation regulates nucleotide excision repair through an interaction with the XPC protein.

  Masayuki Kusakabe, Erina Kakumu, Fumika Kurihara, Kazuki Tsuchida, Takumi Maeda, Haruto Tada, Kanako Kusao, Akari Kato, Takeshi Yasuda, Tomonari Matsuda, Mitsuyoshi Nakao, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa

  The XPC protein complex plays a central role in DNA lesion recognition for global genome nucleotide excision repair (GG-NER). Lesion recognition can be accomplished in either a UV-DDB-dependent or -independent manner; however, it is unclear how these sub-pathways are regulated in chromatin. Here, we show that histone deacetylases 1 and 2 facilitate UV-DDB-independent recruitment of XPC to DNA damage by inducing histone deacetylation. XPC localizes to hypoacetylated chromatin domains in a DNA damage-independent manner, mediated by its structurally disordered middle (M) region. The M region interacts directly with the N-terminal tail of histone H3, an interaction compromised by H3 acetylation. Although the M region is dispensable for in vitro NER, it promotes DNA damage removal by GG-NER in vivo, particularly in the absence of UV-DDB. We propose that histone deacetylation around DNA damage facilitates the recruitment of XPC through the M region, contributing to efficient lesion recognition and initiation of GG-NER.

  Apr. 2022, iScience, 25(4) (4), 104040 - 104040, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Functional impacts of the ubiquitin-proteasome system on DNA damage recognition in global genome nucleotide excision repair.

  Wataru Sakai, Mayumi Yuasa-Sunagawa, Masayuki Kusakabe, Aiko Kishimoto, Takeshi Matsui, Yuki Kaneko, Jun-Ichi Akagi, Nicolas Huyghe, Masae Ikura, Tsuyoshi Ikura, Fumio Hanaoka, Masayuki Yokoi, Kaoru Sugasawa

  The ubiquitin-proteasome system (UPS) plays crucial roles in regulation of various biological processes, including DNA repair. In mammalian global genome nucleotide excision repair (GG-NER), activation of the DDB2-associated ubiquitin ligase upon UV-induced DNA damage is necessary for efficient recognition of lesions. To date, however, the precise roles of UPS in GG-NER remain incompletely understood. Here, we show that the proteasome subunit PSMD14 and the UPS shuttle factor RAD23B can be recruited to sites with UV-induced photolesions even in the absence of XPC, suggesting that proteolysis occurs at DNA damage sites. Unexpectedly, sustained inhibition of proteasome activity results in aggregation of PSMD14 (presumably with other proteasome components) at the periphery of nucleoli, by which DDB2 is immobilized and sequestered from its lesion recognition functions. Although depletion of PSMD14 alleviates such DDB2 immobilization induced by proteasome inhibitors, recruitment of DDB2 to DNA damage sites is then severely compromised in the absence of PSMD14. Because all of these proteasome dysfunctions selectively impair removal of cyclobutane pyrimidine dimers, but not (6-4) photoproducts, our results indicate that the functional integrity of the proteasome is essential for the DDB2-mediated lesion recognition sub-pathway, but not for GG-NER initiated through direct lesion recognition by XPC.

  Lead, Nov. 2020, Scientific reports, 10(1) (1), 19704 - 19704, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Mechanism and regulation of DNA damage recognition in nucleotide excision repair.

  Masayuki Kusakabe, Yuki Onishi, Haruto Tada, Fumika Kurihara, Kanako Kusao, Mari Furukawa, Shigenori Iwai, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa

  Nucleotide excision repair (NER) is a versatile DNA repair pathway, which can remove an extremely broad range of base lesions from the genome. In mammalian global genomic NER, the XPC protein complex initiates the repair reaction by recognizing sites of DNA damage, and this depends on detection of disrupted/destabilized base pairs within the DNA duplex. A model has been proposed that XPC first interacts with unpaired bases and then the XPD ATPase/helicase in concert with XPA verifies the presence of a relevant lesion by scanning a DNA strand in 5'-3' direction. Such multi-step strategy for damage recognition would contribute to achieve both versatility and accuracy of the NER system at substantially high levels. In addition, recognition of ultraviolet light (UV)-induced DNA photolesions is facilitated by the UV-damaged DNA-binding protein complex (UV-DDB), which not only promotes recruitment of XPC to the damage sites, but also may contribute to remodeling of chromatin structures such that the DNA lesions gain access to XPC and the following repair proteins. Even in the absence of UV-DDB, however, certain types of histone modifications and/or chromatin remodeling could occur, which eventually enable XPC to find sites with DNA lesions. Exploration of novel factors involved in regulation of the DNA damage recognition process is now ongoing.

  BMC, 2019, Genes and environment : the official journal of the Japanese Environmental Mutagen Society, 41, 2 - 2, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Importance of finding the bona fide target of the Fanconi anemia pathway.

  Wataru Sakai, Kaoru Sugasawa

  Fanconi anemia (FA) is a rare genetic disease characterized by the deficiency of the cellular response and repair pathway for DNA interstrand crosslink (ICL) damage. Although recent studies have revealed the detailed molecular functions of FA proteins encoded by 22 genes, the mechanism of occurrence of endogenous ICLs in the human body remains poorly understood. In this short review, we summarize the potential endogenous sources of ICLs counteracted by FA proteins, and provide perspectives on the unanswered questions regarding FA.

  2019, Genes and environment : the official journal of the Japanese Environmental Mutagen Society, 41, 6 - 6, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Thymine DNA glycosylase modulates DNA damage response and gene expression by base excision repair-dependent and independent mechanisms.

  Tomohumi Nakamura, Kouichi Murakami, Haruto Tada, Yoshihiko Uehara, Jumpei Nogami, Kazumitsu Maehara, Yasuyuki Ohkawa, Hisato Saitoh, Hideo Nishitani, Tetsuya Ono, Ryotaro Nishi, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa

  Thymine DNA glycosylase (TDG) is a base excision repair (BER) enzyme, which is implicated in correction of deamination-induced DNA mismatches, the DNA demethylation process and regulation of gene expression. Because of these pivotal roles associated, it is crucial to elucidate how the TDG functions are appropriately regulated in vivo. Here, we present evidence that the TDG protein undergoes degradation upon various types of DNA damage, including ultraviolet light (UV). The UV-induced degradation of TDG was dependent on proficiency in nucleotide excision repair and on CRL4CDT2 -mediated ubiquitination that requires a physical interaction between TDG and DNA polymerase clamp PCNA. Using the Tdg-deficient mouse embryonic fibroblasts, we found that ectopic expression of TDG compromised cellular survival after UV irradiation and repair of UV-induced DNA lesions. These negative effects on cellular UV responses were alleviated by introducing mutations in TDG that impaired its BER function. The expression of TDG induced a large-scale alteration in the gene expression profile independently of its DNA glycosylase activity, whereas a subset of genes was affected by the catalytic activity of TDG. Our results indicate the presence of BER-dependent and BER-independent functions of TDG, which are involved in regulation of cellular DNA damage responses and gene expression patterns.

  WILEY, Apr. 2017, Genes to cells : devoted to molecular & cellular mechanisms, 22(4) (4), 392 - 405, English, International magazine

  [Refereed]

  Scientific journal


• Xeroderma pigmentosum group C protein interacts with histones: regulation by acetylated states of histone H3.

  Erina Kakumu, Seiya Nakanishi, Hiromi M Shiratori, Akari Kato, Wataru Kobayashi, Shinichi Machida, Takeshi Yasuda, Naoko Adachi, Naoaki Saito, Tsuyoshi Ikura, Hitoshi Kurumizaka, Hiroshi Kimura, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa

  In the mammalian global genome nucleotide excision repair pathway, two damage recognition factors, XPC and UV-DDB, play pivotal roles in the initiation of the repair reaction. However, the molecular mechanisms underlying regulation of the lesion recognition process in the context of chromatin structures remain to be understood. Here, we show evidence that damage recognition factors tend to associate with chromatin regions devoid of certain types of acetylated histones. Treatment of cells with histone deacetylase inhibitors retarded recruitment of XPC to sites of UV-induced DNA damage and the subsequent repair process. Biochemical studies showed novel multifaceted interactions of XPC with histone H3, which were profoundly impaired by deletion of the N-terminal tail of histone H3. In addition, histone H1 also interacted with XPC. Importantly, acetylation of histone H3 markedly attenuated the interaction with XPC in vitro, and local UV irradiation of cells decreased the level of H3K27ac in the damaged areas. Our results suggest that histone deacetylation plays a significant role in the process of DNA damage recognition for nucleotide excision repair and that the localization and functions of XPC can be regulated by acetylated states of histones.

  WILEY, Mar. 2017, Genes to cells : devoted to molecular & cellular mechanisms, 22(3) (3), 310 - 327, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Mismatch repair proteins recruited to ultraviolet light-damaged sites lead to degradation of licensing factor Cdt1 in the G1 phase

  Miyuki Tanaka, Michiyo Takahara, Kohei Nukina, Akiyo Hayashi, Wataru Sakai, Kaoru Sugasawa, Yasushi Shiomi, Hideo Nishitani

  Cdt1 is rapidly degraded by CRL4(Cdt2) E3 ubiquitin ligase after UV (UV) irradiation. Previous reports revealed that the nucleotide excision repair (NER) pathway is responsible for the rapid Cdt1-proteolysis. Here, we show that mismatch repair (MMR) proteins are also involved in the degradation of Cdt1 after UV irradiation in the G1 phase. First, compared with the rapid (within approximate to 15min) degradation of Cdt1 in normal fibroblasts, Cdt1 remained stable for approximate to 30min in NER-deficient XP-A cells, but was degraded within approximate to 60min. The delayed degradation was also dependent on PCNA and CRL4(Cdt2). The MMR proteins Msh2 and Msh6 were recruited to the UV-damaged sites of XP-A cells in the G1 phase. Depletion of these factors with small interfering RNAs prevented Cdt1 degradation in XP-A cells. Similar to the findings in XP-A cells, depletion of XPA delayed Cdt1 degradation in normal fibroblasts and U2OS cells, and co-depletion of Msh6 further prevented Cdt1 degradation. Furthermore, depletion of Msh6 alone delayed Cdt1 degradation in both cell types. When Cdt1 degradation was attenuated by high Cdt1 expression, repair synthesis at the damaged sites was inhibited. Our findings demonstrate that UV irradiation induces multiple repair pathways that activate CRL4(Cdt2) to degrade its target proteins in the G1 phase of the cell cycle, leading to efficient repair of DNA damage.

  TAYLOR & FRANCIS INC, 2017, CELL CYCLE, 16(7) (7), 673 - 684, English

  [Refereed]

  Scientific journal


• A 10-year follow-up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole-genome sequencing.

  Ryusuke Ono, Taro Masaki, Franklin Mayca Pozo, Yuka Nakazawa, Sigrid M A Swagemakers, Eiji Nakano, Wataru Sakai, Seiji Takeuchi, Fumio Kanda, Tomoo Ogi, Peter J van der Spek, Kaoru Sugasawa, Chikako Nishigori

  BACKGROUND: Most patients with xeroderma pigmentosum complementation group D (XP-D) from Western countries suffer from neurological symptoms, whereas Japanese patients display only skin manifestations without neurological symptoms. We have previously suggested that these differences in clinical manifestations in XP-D patients are attributed partly to a predominant mutation in ERCC2, and the allele frequency of S541R is highest in Japan. METHODS: We diagnosed a child with mild case of XP-D by the evaluation of DNA repair activity and whole-genome sequencing, and followed her ten years. RESULTS: Skin cancer, mental retardation, and neurological symptoms were not observed. Her minimal erythema dose was 41 mJ/cm(2) , which was slightly lower than that of healthy Japanese volunteers. The patient's cells showed sixfold hypersensitivity to UV in comparison with normal cells. Post-UV unscheduled DNA synthesis was 20.4%, and post-UV recovery of RNA synthesis was 58% of non-irradiated samples, which was lower than that of normal fibroblasts. Genome sequence analysis indicated that the patient harbored a compound heterozygous mutation of c.1621A>C and c.591_594del, resulting in p.S541R and p.Y197* in ERCC2: then, patient was diagnosed with XP-D. Y197* has not been described before. CONCLUSION: Her mild skin manifestations might be attributed to the mutational site on her genome and daily strict sun protection. c.1621A>C might be a founder mutation of ERCC2 among Japanese XP-D patients, as it was identified most frequently in Japanese XP-D patients and it has not been found elsewhere outside Japan.

  Jul. 2016, Photodermatology, photoimmunology & photomedicine, 32(4) (4), 174 - 80, English, International magazine

  [Refereed]

  Scientific journal


• SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair.

  Masaki Akita, Yon-Soo Tak, Tsutomu Shimura, Syota Matsumoto, Yuki Okuda-Shimizu, Yuichiro Shimizu, Ryotaro Nishi, Hisato Saitoh, Shigenori Iwai, Toshio Mori, Tsuyoshi Ikura, Wataru Sakai, Fumio Hanaoka, Kaoru Sugasawa

  The xeroderma pigmentosum group C (XPC) protein complex is a key factor that detects DNA damage and initiates nucleotide excision repair (NER) in mammalian cells. Although biochemical and structural studies have elucidated the interaction of XPC with damaged DNA, the mechanism of its regulation in vivo remains to be understood in more details. Here, we show that the XPC protein undergoes modification by small ubiquitin-related modifier (SUMO) proteins and the lack of this modification compromises the repair of UV-induced DNA photolesions. In the absence of SUMOylation, XPC is normally recruited to the sites with photolesions, but then immobilized profoundly by the UV-damaged DNA-binding protein (UV-DDB) complex. Since the absence of UV-DDB alleviates the NER defect caused by impaired SUMOylation of XPC, we propose that this modification is critical for functional interactions of XPC with UV-DDB, which facilitate the efficient damage handover between the two damage recognition factors and subsequent initiation of NER.

  Jun. 2015, Scientific reports, 5(5) (5), 10984 - 10984, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein.

  Syota Matsumoto, Eric S Fischer, Takeshi Yasuda, Naoshi Dohmae, Shigenori Iwai, Toshio Mori, Ryotaro Nishi, Ken-ichi Yoshino, Wataru Sakai, Fumio Hanaoka, Nicolas H Thomä, Kaoru Sugasawa

  In mammalian nucleotide excision repair, the DDB1-DDB2 complex recognizes UV-induced DNA photolesions and facilitates recruitment of the XPC complex. Upon binding to damaged DNA, the Cullin 4 ubiquitin ligase associated with DDB1-DDB2 is activated and ubiquitinates DDB2 and XPC. The structurally disordered N-terminal tail of DDB2 contains seven lysines identified as major sites for ubiquitination that target the protein for proteasomal degradation; however, the precise biological functions of these modifications remained unknown. By exogenous expression of mutant DDB2 proteins in normal human fibroblasts, here we show that the N-terminal tail of DDB2 is involved in regulation of cellular responses to UV. By striking contrast with behaviors of exogenous DDB2, the endogenous DDB2 protein was stabilized even after UV irradiation as a function of the XPC expression level. Furthermore, XPC competitively suppressed ubiquitination of DDB2 in vitro, and this effect was significantly promoted by centrin-2, which augments the DNA damage-recognition activity of XPC. Based on these findings, we propose that in cells exposed to UV, DDB2 is protected by XPC from ubiquitination and degradation in a stochastic manner; thus XPC allows DDB2 to initiate multiple rounds of repair events, thereby contributing to the persistence of cellular DNA repair capacity.

  Feb. 2015, Nucleic acids research, 43(3) (3), 1700 - 13, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• FANCD2 is a target for caspase 3 during DNA damage-induced apoptosis.

  Wataru Sakai, Kaoru Sugasawa

  The Fanconi anemia (FA) pathway, of which the FANCD2 protein is a key component, plays crucial roles in the maintenance of hematopoietic stem cells and suppression of carcinogenesis. However, the function of FANCD2 remains unclear. Here, we report that FANCD2 is a novel and specific substrate of caspase 3. Cleavage of FANCD2 by caspase 3 did not require either the FA core complex or mono-ubiquitylation of FANCD2, and was stimulated by p53. In addition, we identified the cleavage sites and generated cell lines that stably express a caspase-resistant FANCD2 mutant. Our data suggest that FANCD2 is regulated by caspase-mediated degradation during apoptosis induced by DNA damage.

  ELSEVIER SCIENCE BV, Oct. 2014, FEBS letters, 588(20) (20), 3778 - 85, English, International magazine

  [Refereed]

  Scientific journal


• FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair.

  Junya Unno, Akiko Itaya, Masato Taoka, Koichi Sato, Junya Tomida, Wataru Sakai, Kaoru Sugasawa, Masamichi Ishiai, Tsuyoshi Ikura, Toshiaki Isobe, Hitoshi Kurumizaka, Minoru Takata

  The Fanconi anemia (FA) pathway is critically involved in the maintenance of hematopoietic stem cells and the suppression of carcinogenesis. A key FA protein, FANCD2, is monoubiquitinated and accumulates in chromatin in response to DNA interstrand crosslinks (ICLs), where it coordinates DNA repair through mechanisms that are still poorly understood. Here, we report that CtIP protein directly interacts with FANCD2. A region spanning amino acids 166 to 273 of CtIP and monoubiquitination of FANCD2 are both essential for the FANCD2-CtIP interaction and mitomycin C (MMC)-induced CtIP foci. Remarkably, both FANCD2 and CtIP are critical for MMC-induced RPA2 hyperphosphorylation, an event that accompanies end resection of double-strand breaks. Collectively, our results reveal a role of monoubiquitinated FANCD2 in end resection that depends on its binding to CtIP during ICL repair.

  CELL PRESS, May 2014, Cell reports, 7(4) (4), 1039 - 47, English, International magazine

  [Refereed]

  Scientific journal


• Structure-function analysis of the EF-hand protein centrin-2 for its intracellular localization and nucleotide excision repair.

  Ryotaro Nishi, Wataru Sakai, Daisuke Tone, Fumio Hanaoka, Kaoru Sugasawa

  Centrin-2 is an evolutionarily conserved, calmodulin-related protein, which is involved in multiple cellular functions including centrosome regulation and nucleotide excision repair (NER) of DNA. Particularly to exert the latter function, complex formation with the XPC protein, the pivotal NER damage recognition factor, is crucial. Here, we show that the C-terminal half of centrin-2, containing two calcium-binding EF-hand motifs, is necessary and sufficient for both its localization to the centrosome and interaction with XPC. In XPC-deficient cells, nuclear localization of overexpressed centrin-2 largely depends on co-overexpression of XPC, and mutational analyses of the C-terminal domain suggest that XPC and the major binding partner in the centrosome share a common binding surface on the centrin-2 molecule. On the other hand, the N-terminal domain of centrin-2 also contains two EF-hand motifs but shows only low-binding affinity for calcium ions. Although the N-terminal domain is dispensable for enhancement of the DNA damage recognition activity of XPC, it contributes to augmenting rather weak physical interaction between XPC and XPA, another key factor involved in NER. These results suggest that centrin-2 may have evolved to bridge two protein factors, one with high affinity and the other with low affinity, thereby allowing delicate regulation of various biological processes.

  Lead, Aug. 2013, Nucleic acids research, 41(14) (14), 6917 - 29, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas.

  Barbara Norquist, Kaitlyn A Wurz, Christopher C Pennil, Rochelle Garcia, Jenny Gross, Wataru Sakai, Beth Y Karlan, Toshiyasu Taniguchi, Elizabeth M Swisher

  PURPOSE: Secondary somatic BRCA1/2 mutations may restore BRCA1/2 protein in hereditary ovarian carcinomas. In cell lines, BRCA2 restoration mediates resistance to platinum chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors. We assessed primary and recurrent BRCA1/2-mutated ovarian carcinomas to define the frequency of secondary mutations and correlate these changes with clinical outcomes. METHODS: Neoplastic cells were isolated with laser capture microdissection, and DNA was sequenced at the site of the known germline BRCA1/2 mutation. When secondary mutations were found that restored wild-type sequence, haplotyping was performed using single nucleotide polymorphisms in tumor and paired lymphocyte DNA to rule out retention of the wild-type allele. RESULTS: There were 64 primary and 46 recurrent ovarian carcinomas assessed. Thirteen (28.3%) of 46 (95% CI, 17.3% to 42.6%) recurrent carcinomas had a secondary mutation compared with two (3.1%) of 64 (95% CI, 1.0% to 10.7%) primary carcinomas (P = .0003, Fisher's exact test). Twelve (46.2%) of 26 (95% CI, 28.7% to 64.7%) platinum-resistant recurrences had secondary mutations restoring BRCA1/2, compared with one (5.3%) of 19 (95% CI, 1.2% to 24.8%) platinum-sensitive recurrences (P = .003, Fisher's exact test). Six (66.7%) of nine (95% CI, 34.8% to 87.8%) women with prior breast carcinoma had a recurrent carcinoma with a secondary mutation, compared with six (17.1%) of 35 (95% CI, 8.2% to 32.8%) with no history of breast carcinoma (P = .007, Fisher's exact test). CONCLUSION: Secondary somatic mutations that restore BRCA1/2 in carcinomas from women with germline BRCA1/2 mutations predict resistance to platinum chemotherapy and may also predict resistance to PARP inhibitors. These mutations were detectable only in ovarian carcinomas of women whom have had previous chemotherapy, either for ovarian or breast carcinoma.

  Aug. 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 29(22) (22), 3008 - 15, English, International magazine

  [Refereed]


• The epistatic relationship between BRCA2 and the other RAD51 mediators in homologous recombination.

  Yong Qing, Mitsuyoshi Yamazoe, Kouji Hirota, Donniphat Dejsuphong, Wataru Sakai, Kimiyo N Yamamoto, Douglas K Bishop, XiaoHua Wu, Shunichi Takeda

  RAD51 recombinase polymerizes at the site of double-strand breaks (DSBs) where it performs DSB repair. The loss of RAD51 causes extensive chromosomal breaks, leading to apoptosis. The polymerization of RAD51 is regulated by a number of RAD51 mediators, such as BRCA1, BRCA2, RAD52, SFR1, SWS1, and the five RAD51 paralogs, including XRCC3. We here show that brca2-null mutant cells were able to proliferate, indicating that RAD51 can perform DSB repair in the absence of BRCA2. We disrupted the BRCA1, RAD52, SFR1, SWS1, and XRCC3 genes in the brca2-null cells. All the resulting double-mutant cells displayed a phenotype that was very similar to that of the brca2-null cells. We suggest that BRCA2 might thus serve as a platform to recruit various RAD51 mediators at the appropriate position at the DNA-damage site.

  Jul. 2011, PLoS genetics, 7(7) (7), e1002148, English, International magazine

  [Refereed]


• Functional restoration of BRCA2 protein by secondary BRCA2 mutations in BRCA2-mutated ovarian carcinoma.

  Wataru Sakai, Elizabeth M Swisher, Céline Jacquemont, Kurapaty Venkatapoorna Chandramohan, Fergus J Couch, Simon P Langdon, Kaitlyn Wurz, Jake Higgins, Emily Villegas, Toshiyasu Taniguchi

  Acquired platinum resistance is a serious problem in the treatment of ovarian carcinomas. However, the mechanism of the drug resistance has not been elucidated. Here, we show functional significance of restoration of BRCA2 protein by secondary BRCA2 mutations in acquired drug resistance of BRCA2-mutated ovarian carcinoma. Three ovarian cancer cell lines (PEO1, PEO4, and PEO6) were derived from a BRCA2 mutation [5193C>G (Y1655X)] carrier with ovarian carcinoma with acquired cisplatin resistance and a secondary BRCA2 mutation [5193C>T (Y1655Y)] that canceled the inherited mutation. PEO1 was BRCA2 deficient and sensitive to cisplatin and a poly(ADP-ribose) polymerase inhibitor, AG14361, whereas PEO4 was resistant. PEO4 and PEO6, derived from ascites at the time of relapse with cisplatin resistance, had the secondary mutation and were BRCA2 proficient. In vitro cisplatin/AG14361 selection of PEO1 led to restoration of BRCA2 due to another secondary BRCA2 mutation. BRCA2 depletion sensitized BRCA2-restored PEO1 clones and PEO4 to cisplatin/AG14361. Thus, restoration of BRCA2 due to secondary BRCA2 mutation is involved in acquired drug resistance of BRCA2-mutated ovarian carcinoma.

  Lead, Aug. 2009, Cancer research, 69(16) (16), 6381 - 6, English, International magazine

  [Refereed]

  Scientific journal


• DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion.

  Hayato Oka, Wataru Sakai, Eiichiro Sonoda, Jun Nakamura, Kenjiro Asagoshi, Samuel H Wilson, Masahiko Kobayashi, Kenichi Yamamoto, Jörg Heierhorst, Shunichi Takeda, Yoshihito Taniguchi

  ASCIZ (ATMIN) was recently identified as a novel DNA damage response protein. Here we report that ASCIZ-deficient chicken DT40 B lymphocyte lines displayed markedly increased Ig gene conversion rates, whereas overexpression of human ASCIZ reduced Ig gene conversion below wild-type levels. However, neither the efficiency of double-strand break repair nor hypermutation was affected by ASCIZ levels, indicating that ASCIZ does not directly control homologous recombination or formation of abasic sites. Loss of ASCIZ led to mild sensitivity to the base damaging agent methylmethane sulfonate (MMS), yet remarkably, suppressed the dramatic MMS hypersensitivity of polbeta-deficient cells. These data suggest that ASCIZ may affect the choice between competing base repair pathways in a manner that reduces the amount of substrates available for Ig gene conversion.

  Jun. 2008, Biochemical and biophysical research communications, 371(2) (2), 225 - 9, English, International magazine

  [Refereed]


• Secondary BRCA1 mutations in BRCA1-mutated ovarian carcinomas with platinum resistance.

  Elizabeth M Swisher, Wataru Sakai, Beth Y Karlan, Kaitlyn Wurz, Nicole Urban, Toshiyasu Taniguchi

  Although ovarian carcinomas with mutated BRCA1 or BRCA2 are sensitive to platinum compounds, such carcinomas eventually develop platinum resistance. Previously, we showed that acquired resistance to cisplatin in BRCA2-mutated tumors can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. Here, we show that secondary mutations of BRCA1 also occur in BRCA1-mutated ovarian cancer with platinum resistance. We evaluated nine recurrent BRCA1-mutated ovarian cancers previously treated with platinum compounds, including five with acquired platinum resistance, one with primary platinum resistance, and three with platinum sensitivity. Four of the six recurrent platinum-resistant tumors had developed secondary genetic changes in BRCA1 that restored the reading frame of the BRCA1 protein, whereas none of the three platinum-sensitive recurrent tumors developed BRCA1 sequence alterations. We immunohistochemically confirmed restored expression of BRCA1 protein in two cases with secondary mutations. Intriguingly, the case with primary platinum resistance showed back mutation of BRCA1 in the primary tumor and showed another secondary mutation in the recurrent tumor. Our results suggest that secondary mutations in BRCA1 can mediate resistance to platinum in BRCA1-mutated ovarian tumors.

  Lead, Apr. 2008, Cancer research, 68(8) (8), 2581 - 6, English, International magazine

  [Refereed]


• Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers.

  Wataru Sakai, Elizabeth M Swisher, Beth Y Karlan, Mukesh K Agarwal, Jake Higgins, Cynthia Friedman, Emily Villegas, Céline Jacquemont, Daniel J Farrugia, Fergus J Couch, Nicole Urban, Toshiyasu Taniguchi

  Ovarian carcinomas with mutations in the tumour suppressor BRCA2 are particularly sensitive to platinum compounds. However, such carcinomas ultimately develop cisplatin resistance. The mechanism of that resistance is largely unknown. Here we show that acquired resistance to cisplatin can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. First, in a cisplatin-resistant BRCA2-mutated breast-cancer cell line, HCC1428, a secondary genetic change in BRCA2 rescued BRCA2 function. Second, cisplatin selection of a BRCA2-mutated pancreatic cancer cell line, Capan-1 (refs 3, 4), led to five different secondary mutations that restored the wild-type BRCA2 reading frame. All clones with secondary mutations were resistant both to cisplatin and to a poly(ADP-ribose) polymerase (PARP) inhibitor (AG14361). Finally, we evaluated recurrent cancers from patients whose primary BRCA2-mutated ovarian carcinomas were treated with cisplatin. The recurrent tumour that acquired cisplatin resistance had undergone reversion of its BRCA2 mutation. Our results suggest that secondary mutations that restore the wild-type BRCA2 reading frame may be a major clinical mediator of acquired resistance to platinum-based chemotherapy.

  Lead, Feb. 2008, Nature, 451(7182) (7182), 1116 - 20, English, International magazine

  [Refereed]


• Genetic dissection of vertebrate 53BP1: a major role in non-homologous end joining of DNA double strand breaks.

  Kyoko Nakamura, Wataru Sakai, Takuo Kawamoto, Ronan T Bree, Noel F Lowndes, Shunichi Takeda, Yoshihito Taniguchi

  53BP1 (p53 binding protein) is a BRCT domain-containing protein that is rapidly recruited to DNA double strand breaks (DSBs). To investigate the role of 53BP1 in the DNA damage response, we generated 53BP1(-/-) cells from the chicken DT40 cell line. As in mammalian cells, mutation of 53BP1 increased cellular sensitivity to ionizing radiation. Although depletion of 53BP1 resulted in checkpoint defects in mammalian cells, DT40 53BP1(-/-) cells had normal intra S phase and G2/M checkpoints. G1 specific radiosensitivity and a higher sensitivity to topoisomerase II suggested defective non-homologous end joining (NHEJ) defects in DT40 53BP1(-/-) cells. Genetic analyses confirm this suggestion as we have demonstrated an epistatic relationship between 53BP1 and the NHEJ genes, Ku70 and Artemis, but not with Rad54, a gene essential for repair of DSBs by homologous recombination. We conclude that the major role of 53BP1 in supporting survival of DT40 cells that have suffered DNA DSBs is in facilitating repair by NHEJ.

  Jun. 2006, DNA repair, 5(6) (6), 741 - 9, English, International magazine

  [Refereed]


• Lessons from the genome sequence of Neurospora crassa: tracing the path from genomic blueprint to multicellular organism.

  Katherine A Borkovich, Lisa A Alex, Oded Yarden, Michael Freitag, Gloria E Turner, Nick D Read, Stephan Seiler, Deborah Bell-Pedersen, John Paietta, Nora Plesofsky, Michael Plamann, Marta Goodrich-Tanrikulu, Ulrich Schulte, Gertrud Mannhaupt, Frank E Nargang, Alan Radford, Claude Selitrennikoff, James E Galagan, Jay C Dunlap, Jennifer J Loros, David Catcheside, Hirokazu Inoue, Rodolfo Aramayo, Michael Polymenis, Eric U Selker, Matthew S Sachs, George A Marzluf, Ian Paulsen, Rowland Davis, Daniel J Ebbole, Alex Zelter, Eric R Kalkman, Rebecca O'Rourke, Frederick Bowring, Jane Yeadon, Chizu Ishii, Keiichiro Suzuki, Wataru Sakai, Robert Pratt

  We present an analysis of over 1,100 of the approximately 10,000 predicted proteins encoded by the genome sequence of the filamentous fungus Neurospora crassa. Seven major areas of Neurospora genomics and biology are covered. First, the basic features of the genome, including the automated assembly, gene calls, and global gene analyses are summarized. The second section covers components of the centromere and kinetochore complexes, chromatin assembly and modification, and transcription and translation initiation factors. The third area discusses genome defense mechanisms, including repeat induced point mutation, quelling and meiotic silencing, and DNA repair and recombination. In the fourth section, topics relevant to metabolism and transport include extracellular digestion; membrane transporters; aspects of carbon, sulfur, nitrogen, and lipid metabolism; the mitochondrion and energy metabolism; the proteasome; and protein glycosylation, secretion, and endocytosis. Environmental sensing is the focus of the fifth section with a treatment of two-component systems; GTP-binding proteins; mitogen-activated protein, p21-activated, and germinal center kinases; calcium signaling; protein phosphatases; photobiology; circadian rhythms; and heat shock and stress responses. The sixth area of analysis is growth and development; it encompasses cell wall synthesis, proteins important for hyphal polarity, cytoskeletal components, the cyclin/cyclin-dependent kinase machinery, macroconidiation, meiosis, and the sexual cycle. The seventh section covers topics relevant to animal and plant pathogenesis and human disease. The results demonstrate that a large proportion of Neurospora genes do not have homologues in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. The group of unshared genes includes potential new targets for antifungals as well as loci implicated in human and plant physiology and disease.

  Mar. 2004, Microbiology and molecular biology reviews : MMBR, 68(1) (1), 1 - 108, English, International magazine

  [Refereed]


• Isolation and genetic characterization of the Neurospora crassa REV1 and REV7 homologs: evidence for involvement in damage-induced mutagenesis.

  Wataru Sakai, Yuusaku Wada, Yasuko Naoi, Chizu Ishii, Hirokazu Inoue

  In a previous paper, we reported that the Neurospora crassa upr-1 gene is a homolog of the yeast gene REV3, which encodes the catalytic subunit of DNA polymerase zeta (polzeta). Characterization of the upr-1 mutant indicated that the UPR1 protein plays a role in DNA repair and mutagenesis. To help understand the mechanisms of mutagenic DNA repair in the N. crassa more extensively, we identified N. crassa homologs of yeast REV1 and REV7 and obtained mutants ncrev1 or ncrev7, which had similar phenotypes to the upr-1 mutant. Mutant carrying ncrev7 was more sensitive to UV and 4NQO, and slightly sensitive to MMS than the wild-type. The sensitivity to UV and MMS of the ncrev1 mutant was moderately higher than that of the wild-type, but the sensitivity to 4NQO of the mutant was similar to that of the wild-type. In reversion assay using testers with base substitution or frameshift mutation at the ad-3A locus, each of ncrev1 and ncrev7 mutants showed lower induced-mutability than the wild-type. Expression of ncrev1 and ncrev7 was found to be UV-inducible like the case of upr-1. Genetic analyses showed that the ncrev7 was identical to mus-26, which belongs to the upr-1 epistasis group, and that the ncrev1 was a newly identified DNA repair gene and designated as mus-42. Interestingly, all three mutants have a normal CPD photolyase gene, however, they showed a partial photoreactivation defect (PPD) phenotype, not completely defective but inefficient in photoreactivation. These results suggest that N. crassa REV homolog genes function in DNA repair and UV mutagenesis through the bypass of (6-4) photoproducts.

  Lead, Mar. 2003, DNA repair, 2(3) (3), 337 - 46, English, International magazine

  [Refereed]


• The upr-1 gene encodes a catalytic subunit of the DNA polymerase zeta which is involved in damage-induced mutagenesis in Neurospora crassa.

  W Sakai, C Ishii, H Inoue

  The upr-1 mutant was one of the first mutagen-sensitive mutants to be isolated in Neurospora crassa. However, the function of the upr-1 gene has not yet been elucidated, although some genetic and biochemical data have been accumulated. In order to clone the upr-1 gene, we performed a chromosome walk from the mat locus, the closest genetic marker to upr-1 for which a molecular probe was available, towards the centromere, and a chromosomal contig of about 300-400 kb was constructed. Some of these clones complemented the temperature sensitivity of the un-16 mutation, which is located between mat and upr-1. The un-16 gene was sequenced, and localized in the MIPS Neurospora crassa genome database. We then searched the regions flanking un-16 for homologs of known DNA repair genes, and found a gene homologous to the REV3 gene of budding yeast. The phenotype of the upr-1 mutant is similar to that of the yeast rev3 mutant. An ncrev3 mutant carrying mutations in the N. crassa REV3 homolog was constructed using the RIP (repeat-induced point mutation) process. The spectrum of mutagen sensitivity of the ncrev3 mutant was similar to that of the upr-1 mutant. Complementation tests between the upr-1 and ncrev3 mutations indicated that the upr-1 gene is in fact identical to the ncrev3 gene. To clarify the role of the upr-1 gene in DNA repair, the frequency of MMS and 4NQO-induced mutations was assayed using the ad-8 reversion test. The upr-1 mutant was about 10 times less sensitive to both chemicals than the wild type. The expression level of the upr-1 gene is increased on exposure to UV irradiation in the uvs-2 and mus-8 mutants, which belong to postreplication repair group, as well as in the wild type. All these results suggest that the product of the upr-1 gene functions in damage-induced mutagenesis and DNA translesion synthesis in N. crassa.

  Lead, May 2002, Molecular genetics and genomics : MGG, 267(3) (3), 401 - 8, English, International magazine

  [Refereed]

• DNA damage recognition and repair in mammalian global genome nucleotide excision repair

  Wataru Sakai, Kaoru Sugasawa

  The intrinsic instability of genomic DNA renders it susceptible to damage by spontaneously produced by-products such as reactive oxygen species and aldehyde metabolites or environmental genotoxins such as radiation and chemicals. Unrepaired DNA damage interferes with essential DNA transactions, such as replication and transcription, and eventually gives rise to the alteration of genetic information. Because genomic instability can cause cell death or carcinogenesis, DNA damage must be recognized and repaired as quickly as possible. Several mechanisms of DNA repair that function according to the type of damage underlie a highly sensitive system capable of detecting a few sites of damage among the large amount of normal DNA in the genome. Nucleotide excision repair (NER) is a major DNA repair pathway that can eliminate a wide spectrum of damage. In mammals, NER is executed by two subpathways: global genome repair (GGR) and transcription-coupled repair. Both subpathways share common core NER factors but possess unique systems for recognizing DNA damage. Transcription-coupled repair is initiated by the stalling of RNA polymerase II and is responsible for the accelerated repair of DNA damage in the transcribed strand of active genes. By contrast, GGR is initiated by xeroderma pigmentosum group C (XPC) and/or the UV-damaged DNA-binding protein (UV-DDB) complex, followed by the sequential actions of other NER-associated factors. This chapter reviews the molecular mechanisms underlying the recognition and repair of DNA damage by mammalian GGR.

  Springer Japan, 01 Jan. 2016, DNA Replication, Recombination, and Repair: Molecular Mechanisms and Pathology, 155 - 174, English

  [Refereed][Invited]

  Introduction other


• Studies on the de-ubiquitination mechanism for the xeroderma pigmentosum group C protein in UV damage response

  Wataru Sakai, Aiko Kishimoto, Takeshi Matsui, Jun-ichi Akagi, Kaoru Sugasawa

  GENETICS SOC JAPAN, Dec. 2015, GENES & GENETIC SYSTEMS, 90(6) (6), 397 - 397, English

  Summary international conference


• Post-translational modifications coordinating recognition and repair of UV-induced DNA damage

  Syota Matsumoto, Masaki Akita, Wataru Sakai, Kaoru Sugasawa

  ELSEVIER SCIENCE BV, Apr. 2015, DNA REPAIR, 28, 144 - 144, English

  Summary international conference


• Studies on the de-ubiquitylation mechanism of the xeroderma pigmentosum group C protein

  Aiko Kishimoto, Junichi Akagi, Takeshi Matsui, Wataru Sakai, Kaoru Sugasawa

  GENETICS SOC JAPAN, Dec. 2014, GENES & GENETIC SYSTEMS, 89(6) (6), 312 - 312, English

  Summary international conference


• 紫外線損傷修復におけるXPCタンパク質の脱ユビキチン化機構の解析

  岸本藍子, 赤木純一, 松井豪志, 酒井恒, 菅澤薫

  31 Aug. 2014, 日本遺伝学会大会プログラム・予稿集, 86th, 99, Japanese


• A novel function of FANCD2 protein in apoptosis signaling

  Wataru Sakai, Kaoru Sugasawa

  GENETICS SOC JAPAN, Dec. 2013, GENES & GENETIC SYSTEMS, 88(6) (6), 361 - 361, English

  Summary international conference


• Studies on the de-ubiquitylation mechanism of the xeroderma pigmentosum group C protein

  Junichi Akagi, Takeshi Matsui, Wataru Sakai, Kaoru Sugasawa

  GENETICS SOC JAPAN, Dec. 2012, GENES & GENETIC SYSTEMS, 87(6) (6), 386 - 386, English

  Summary international conference


• 紫外線損傷修復におけるXPCタンパク質の脱ユビキチン化機構の解析

  赤木純一, 松井豪志, 酒井恒, 菅澤薫

  31 Aug. 2012, 日本遺伝学会大会プログラム・予稿集, 84th, 72, Japanese


• ゲノム安定維持に関わるcentrin-2の新たな機能

  菅澤薫, 菅澤薫, 西良太郎, 酒井恒, 戸根大輔, 戸根大輔, 花岡文雄

  2012, 日本分子生物学会年会プログラム・要旨集(Web), 35th


• Genotoxic stress targets Fanconi anemia group D2 protein for fragmentation by the caspase-mediated pathway

  Wataru Sakai, Kaoru Sugasawa

  GENETICS SOC JAPAN, Feb. 2010, GENES & GENETIC SYSTEMS, 85(1) (1), 86 - 86, English

  Summary international conference


• DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion (vol 371, pg 225, 2008)

  Hayato Oka, Wataru Sakai, Eiichiro Sonoda, Jun Nakamura, Kenjiro Asagoshi, Samuel H. Wilson, Masahiko Kobayashi, Kenichi Yamamoto, Joerg Heierhorst, Shunichi Takeda, Yoshihito Taniguchi

  ACADEMIC PRESS INC ELSEVIER SCIENCE, Dec. 2008, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 377(1) (1), 326 - 326, English

  Others

• 光老化科学の最前線

  酒井 恒, 菅澤 薫

  Joint work, シーエムシー出版, Apr. 2015, Japanese

  Scholarly book

• 脂肪族アルデヒドの代謝異常がゲノム安定性に及ぼす影響

  酒井恒, 䑺谷智也, 梶本武利, 岡田太郎, 篠原正和, 横井雅幸, 菅澤薫

  日本環境変異原ゲノム学会第53回大会, Dec. 2024, Japanese

  [Invited]

  Invited oral presentation


• ヌクレオチド除去修復のDNA損傷認識制御におけるヒストン修飾の役割

  綿田瑞希, 日下部将之, 前田拓海, 各務恵理菜, 横井雅幸, 酒井恒, 菅澤薫

  第47回日本分子生物学会年会, Nov. 2024, Japanese

  Poster presentation


• アルデヒド脱水素酵素ALDH3A2の欠損がゲノム安定性に及ぼす影響

  䑺谷智也, 岡田太郎, 梶本武利, 篠原正和, 横井雅幸, 菅澤薫, 酒井恒

  第47回日本分子生物学会年会, Nov. 2024, Japanese

  Poster presentation


• ヌクレオチド除去修復のDNA損傷認識を制御するクロマチン構造変換機構

  藤原叶枝, 槌田千輝, 日下部将之, 草尾佳那子, 八鍬聖, 横井雅幸, 酒井恒, 菅澤薫

  第47回日本分子生物学会年会, Nov. 2024, Japanese

  Poster presentation


• The involvement of chromatin remodeling factor SMACRAD1 in response to DNA double strand breaks

  Miou Takasu, Masayuki Kusanabe, Atsushi Shibata, Wataru Sakai, Kaoru Sugasawa, Masayuki Yokoi

  The12th 3R+3C International Symposium, Nov. 2024, English

  Poster presentation


• Impact of histone modifications on damage recognition process of global genome nucleotide excision repair

  Masayuki Kusakabe, Mizuki Watada, Takumi Maeda, Erina Kakumu, Kanae Fujiwara, Mizuki Otobe, Wataru Sakai, Masayuki Yokoi, Kaoru Sugasawa

  The12th 3R+3C International Symposium, Nov. 2024, English

  Poster presentation


• ヌクレオチド除去修復の損傷認識制御におけるヒストン修飾の役割

  日下部将之, 綿田瑞希, 前田拓海, 各務恵理菜, 藤原叶枝, 田口萌衣, 酒井恒, 横井雅幸, 菅澤薫

  日本放射線影響学会第67回大会, Sep. 2024, Japanese

  Oral presentation


• 損傷クロマチン基質を用いたヌクレオチド除去修復制御機構の生化学的解析

  古園英嗣, 多田遥人, 日下部将之, 松本翔太, 横井雅幸, 酒井 恒, 鯨井智也, 胡桃坂仁志, 菅澤 薫

  第41回染色体ワークショップ・第22回核ダイナミクス研究会, Jan. 2024, Japanese

  Poster presentation


• ヌクレオチド除去修復の損傷監視制御におけるヒストン修飾の役割

  日下部将之, 綿田瑞希, 前田拓海, 各務恵理菜, 藤原叶枝, 乙部瑞貴, 酒井 恒, 横井雅幸, 菅澤 薫

  第41回染色体ワークショップ・第22回核ダイナミクス研究会, Jan. 2024, Japanese

  Oral presentation


• ヌクレオチド除去修復のDNA損傷認識制御におけるヒストンH3K9メチル化修飾の役割

  綿田瑞希, 日下部将之, 前田拓海, 各務恵理菜, 横井雅幸, 酒井 恒, 菅澤 薫

  第46回日本分子生物学会年会, Dec. 2023, Japanese

  Poster presentation


• 紫外線誘発DNA損傷に対する細胞応答におけるクロマチンリモデリング因⼦SMARCAD1の関与

  高須美央, 坂口友美, 酒井麻衣, 鹿谷有由希, 福永 匠, 酒井 恒, 日下部将之, 菅澤 薫, 花岡文雄, 横井雅幸

  第46回日本分子生物学会年会, Dec. 2023, Japanese

  Poster presentation


• DNAポリメラーゼ‧イータの発現調節における脱ユビキチン化酵素USP11の関与

  中森晴渚, 仲野由佳梨, 案済 萌, 菅野新一郎, 安井 明, 酒井 恒, 菅澤 薫, 花岡文雄, 横井雅幸

  第46回日本分子生物学会年会, Dec. 2023, Japanese

  Poster presentation


• ゲノム全体を対象としたヌクレオチド除去修復の損傷認識を制御するクロマチン動態

  日下部将之, 前田拓海, 綿田瑞希, 藤原叶枝, 各務恵理菜, 乙部瑞貴, 酒井 恒, 横井雅幸, 菅澤 薫

  第46回日本分子生物学会年会, Dec. 2023, Japanese

  Oral presentation


• ヒストン翻訳後修飾を介したXPCタンパク質の核内局在制御

  乙部瑞貴, 日下部将之, 各務恵理菜, 槌田千輝, 塩月陽人, 酒井 恒, 横井雅幸, 菅澤 薫

  第46回日本分子生物学会年会, Dec. 2023, Japanese

  Poster presentation


• ヌクレオチド除去修復のDNA損傷認識を制御するクロマチン構造変換機構

  藤原叶枝, 槌田千輝, 日下部将之, 草尾佳那子, 八鍬 聖, 酒井 恒, 横井雅幸, 菅澤 薫

  第46回日本分子生物学会年会, Dec. 2023, Japanese

  Poster presentation


• 脂肪族アルデヒド脱水素酵素の欠損により生じる細胞毒性の解析

  䑺谷智也, 大槻侑恵, 後藤元成, 笹野真唯子, 松田 俊, 松田知成, 梶本武利, 岡田太郎, 横井雅幸, 菅澤 薫, 酒井 恒

  日本環境変異原ゲノム学会第52回大会, Nov. 2023, Japanese

  Poster presentation


• 脂肪族アルデヒド脱水素酵素のゲノム安定性維持における影響

  酒井 恒, 䑺谷智也, 大槻侑恵, 後藤元成, 笹野真唯子, 松田 俊, 松田知成, 梶本武利, 岡田太郎, 横井雅幸, 菅澤 薫

  日本環境変異原ゲノム学会第52回大会, Nov. 2023, Japanese

  Oral presentation


• 脂質代謝制御におけるファンコニ貧血タンパク質の機能解析

  酒井 恒, 䑺谷智也, 大槻侑恵, 後藤元成, 乾 愛実, 松田 俊, 松田知成, 横井雅幸, 菅澤 薫

  第45回日本分子生物学会年会, Nov. 2022, Japanese

  Poster presentation


• ヌクレオチド除去修復におけるDNA損傷認識を制御するクロマチン構造変換因子複合体

  槌田千輝, 日下部将之, 各務恵理菜, 栗原文佳, 草尾佳那子, 前田拓海, 横井雅幸, 酒井 恒, 菅澤 薫

  第45回日本分子生物学会年会, Nov. 2022, Japanese

  Poster presentation


• 脂質代謝制御におけるファンコニ貧血タンパク質の機能解析

  酒井 恒, 䑺谷智也, 大槻侑恵, 後藤元成, 乾 愛実, 松田 俊, 松田知成, 横井雅幸, 菅澤 薫

  第45回日本分子生物学会年会（幕張）ワークショップ, Nov. 2022, Japanese

  Oral presentation


• ヌクレオチド除去修復における紫外線誘発DNA損傷の効率的な認識に寄与するヒストン修飾

  日下部将之, 前田拓海, 各務恵理菜, 綿田瑞希, 酒井 恒, 横井雅幸, 菅澤 薫

  日本放射線影響学会第65回大会, Sep. 2022, Japanese

  Oral presentation


• 色素性乾皮症C群タンパク質によるDNA損傷認識を制御するクロマチン動態

  前田拓海, 日下部将之, 横井雅幸, 酒井恒, 菅澤薫

  第39回染色体ワークショップ・第20回核ダイナミクス研究会, Dec. 2021, Japanese

  Poster presentation


• ヒストン脱アセチル化はヌクレオチド除去修復におけるDNA損傷認識を制御する

  槌田千輝, 日下部将之, 各務恵理菜, 栗原文佳, 多田遥人, 前田拓海, 横井雅幸, 酒井恒, 菅澤薫

  第39回染色体ワークショップ・第20回核ダイナミクス研究会, Dec. 2021, Japanese

  Poster presentation


• ヒストン脱アセチル化はヌクレオチド除去修復におけるDNA損傷認識を制御する

  槌田千輝, 日下部将之, 各務恵理菜, 栗原文佳, 多田遥人, 前田拓海, 横井雅幸, 酒井 恒, 菅澤 薫

  第44回日本分子生物学会年会, Dec. 2021, Japanese

  Poster presentation


• 脱ユビキチン化酵素による損傷乗り越え合成の制御機構の解析

  仲野由佳梨, 案済萌, 菅野新一郎, 安井明, 酒井恒, 菅澤薫, 花岡文雄, 横井雅幸

  第44回日本分子生物学会年会, Dec. 2021, Japanese

  Poster presentation


• ファンコニ貧血タンパク質の脂質代謝における機能解析

  䑺谷智也, 大槻侑恵, 後藤元成, 乾 愛実, 横井雅幸, 菅澤 薫, 酒井 恒

  第44回日本分子生物学会年会, Dec. 2021, Japanese

  Poster presentation


• 色素性乾皮症C群タンパク質によるDNA損傷認識を制御するクロマチン動態

  前田拓海, 日下部将之, 横井雅幸, 酒井 恒, 菅澤 薫

  第44回日本分子生物学会年会, Dec. 2021, Japanese

  Poster presentation


• ヌクレオチド除去修復におけるDNA損傷認識を制御するクロマチンダイナミクス

  日下部将之, 各務恵理菜, 栗原文佳, 槌田千輝, 多田遥人, 横井雅幸, 酒井 恒, 菅澤 薫

  第94回日本生化学会大会, Nov. 2021, Japanese

  Oral presentation


• 脂質代謝におけるファンコニ貧血タンパク質の機能解析

  酒井恒, 大槻侑恵, 後藤元成, 乾愛実, 䑺谷智也, 横井雅幸, 菅澤薫

  日本環境変異原学会第49回大会, Nov. 2020, Japanese

  Oral presentation


• RNAを介したヌクレオチド除去修復制御機構の解析

  古川真理, 日下部将之, 酒井 恒, 横井雅幸, 菅澤 薫

  第42回日本分子生物学会年会, Japanese

  Poster presentation


• 脂質代謝に応答したファンコニ貧血タンパク質のダイナミクス

  酒井 恒, 乾 愛実, 大槻侑恵, 後藤元成, 横井雅幸, 菅澤 薫

  第42回日本分子生物学会年会, Japanese

  Poster presentation


• ファンコニ貧血タンパク質FANCD2と脂質代謝関連因子の機能的連関の解 析

  大槻侑恵, 後藤元成, 乾 愛実, 松田 俊, 松田知成, 横井雅幸, 菅澤 薫, 酒井 恒

  第42回日本分子生物学会年会, Japanese

  Poster presentation


• DNAポリメラーゼ・イータと脱ユビキチン化酵素の相互作用の解析

  案済 萌, 西村 潤, 菅野新一郎, 安井 明, 酒井 恒, 菅澤 薫, 花岡文雄, 横井雅幸

  第42回日本分子生物学会年会, Japanese

  Poster presentation


• TLSポリメラーゼの損傷部位への導入過程を生細胞イメージングにより解 析する試み

  福永 匠, 尾崎未羽, 佐藤正康, 酒井 恒, 菅澤 薫, 花岡文雄, 横井雅幸

  第42回日本分子生物学会年会, Japanese

  Poster presentation


• XPCタンパク質によるDNA損傷認識の制御とヒストン修飾の役割

  栗原文佳, 日下部将之, 各務恵理菜, 草尾佳那子, 前田拓海, 横井雅幸, 酒井 恒, 菅澤 薫

  第42回日本分子生物学会年会, Japanese

  Poster presentation


• ヌクレオチド除去修復の損傷認識を制御するクロマチン構造変換因子の探 索

  草尾佳那子, 日下部将之, 各務恵理菜, 栗原文佳, 前田拓海, 横井雅幸, 酒井 恒, 菅澤 薫

  第42回日本分子生物学会年会, Japanese

  Poster presentation


• 核内－細胞質における脂肪滴のダイナミクス

  酒井 恒

  第3回オルガネラ・ゾーン研究会, Japanese

  Oral presentation


• Chromatin dynamics regulating DNA lesion recognition in nucleotide excision repair

  Masayuki Kusakabe, Fumika Kurihara, Kanako Kusao, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa

  6th Asian Congress on Environmental Mutagens (ACEM) and 48th Annual Meeting of the Japanese Environmental Mutagen Society (JEMS), English

  Oral presentation


• TLSポリメラーゼの生細胞イメージングとその定量解析への取り組み

  福永 匠, 酒井 恒, 菅澤 薫, 横井雅幸

  サイエンスフロンティア研究発表会, Oct. 2019, Japanese

  Poster presentation


• Dynamics of FANCD2 in response to lipid metabolism.

  Yukie Otsuki, Motonari Goto, Megumi Inui, Masayuki Yokoi, Kaoru Sugasawa, Wataru Sakai

  2019 Fanconi anemia research fund 31st scientific symposium, English

  Poster presentation


• 脂肪族アルデヒド代謝におけるファンコニ貧血タンパク質の機能解析

  酒井 恒, 大槻侑恵, 後藤元成, 乾 愛実, 松田 俊, 松田知成, 菅澤 薫

  日本環境変異原学会第47回大会, Nov. 2018, Japanese, 京都, Domestic conference

  Oral presentation


• ファンコニ貧血タンパク質FANCD2と脂質代謝関連因子の相互作用解析

  大槻侑恵, 後藤元成, 乾 愛実, 松田 俊, 松田 知成, 菅澤 薫, 酒井 恒

  第41回日本分子生物学会年会, Nov. 2018, Japanese, 横浜, Domestic conference

  Poster presentation


• XPCタンパク質によるDNA損傷認識の制御におけるヒストン修飾の役割

  KURIHARA FUMIKA, KUSAKABE MASAYUKI, KATO AKARI, KAKUMU ERINA, NAKANISHI SEIYA, KUSAO KANAKO, OKAWA YASUYUKI, YOKOI MASAYUKI, SAKAI WATARU, SUGASAWA KAORU

  第41回日本分子生物学会年会, Nov. 2018, Japanese, 横浜, Domestic conference

  Poster presentation


• クロマチン構造を介したヌクレオチド除去修復の高次制御機構

  日下部将之, 各務恵理菜, 加藤安佳梨, 栗原文佳, 草尾佳那子, 横井雅幸, 酒井 恒, SUGASAWA KAORU

  第91回生化学会大会, Sep. 2018, Japanese, 京都, Domestic conference

  Oral presentation


• Functional impact of ubiquitin-proteasome system on UV-induced DNA damage response and repair

  酒井 恒, 岸本 藍子, 金子 雄貴, 松井 豪志, 赤木 純一, 菅澤 薫

  日本遺伝学会第90回大会, Sep. 2018, Japanese, 奈良, Domestic conference

  Oral presentation


• メタボリックDNA損傷を抑制する新規メカニズムの可能性について

  酒井 恒

  日本環境変異原学会公開シンポジウム, Jun. 2018, Japanese, 東京, Domestic conference

  [Invited]

  Nominated symposium


• ヌクレオチド除去修復の開始を制御するクロマチン構造の役割

  KATO Akari, KAKUMU Erina, NAKANISHI Seiya, KUSAKABE Masayuki, KURIHARA Fumika, SAKAI Wataru, SUGASAWA Kaoru

  2017年度生命科学系学会合同年次大会, Dec. 2017, Japanese, 神戸国際会議場, Domestic conference

  Oral presentation


• 脂質アルデヒド代謝におけるファンコニ貧血タンパク質の機能解析

  SAKAI Wataru, GOTO Motonari, OTSUKI Yukie, MATSUDA Shun, MATSUDA Tomonari, SUGASAWA Kaoru

  日本環境変異原学会第46回大会, Nov. 2017, Japanese, 一橋大学 一橋講堂, Domestic conference

  Poster presentation


• ユビキチン-プロテアソーム系による紫外線誘発DNA損傷応答制御

  SAKAI Wataru, KISHIMOTO Aiko, KANEKO Yuki, MATSUI Takeshi, AKAGI Junichi, SUGASAWA Kaoru

  第24回DNA複製・組換え・修復ワークショップ, Nov. 2017, Japanese, 長良川国際会議場, Domestic conference

  Oral presentation


• ヌクレオチド除去修復の開始を制御するクロマチン構造の役割

  KATO Akari, KAKUMU Erina, NAKANISHI Seiya, KUSAKABE Masayuki, KURIHARA Fumika, SAKAI Wataru, SUGASAWA Kaoru

  第24回DNA複製・組換え・修復ワークショップ, Nov. 2017, Japanese, 長良川国際会議場, Domestic conference

  Oral presentation


• Fatty aldehyde dehydrogenase as a novel binding partner of FANCD2

  SAKAI Wataru, GOTO Motonari, OTSUKI Yukie, MATSUDA Shun, MATSUDA Tomonari, SUGASAWA Kaoru

  2017 FA Scientific Symposium, Sep. 2017, English, Grand Hyatt Atlanta in Buckhead/Atlanta USA, International conference

  [Invited]

  Invited oral presentation


• タンパク質分解系による紫外線誘発DNA損傷応答制御

  SAKAI WATARU, 岸本 藍子, 金子 雄貴, 松井 豪志, 赤木 純一, SUGASAWA KAORU

  第39回日本分子生物学会年会（MBSJ2016）, Nov. 2016, Japanese, 日本分子生物学会, 横浜, Domestic conference

  Poster presentation


• Functional impact of ubiquitin-proteasome system on UV-induced DNA damage response and repair

  Wataru Sakai, Aiko Kishimoto, Yuki Kaneko, Takeshi Matsui, Jun-ichi Akagi, Kaoru Sugasawa

  The 10th 3R Symposium, Nov. 2016, English, The 10th 3R Symposium Organizing Committee, Matsue, Shimane, Japan, International conference

  Poster presentation


• FANCD2新規相互作用因子の探索と機能解析

  GOTO MOTONARI, 松田 俊, 松田 知成, SUGASAWA KAORU, SAKAI WATARU

  第39回日本分子生物学会年会（MBSJ2016）, Nov. 2016, Japanese, 日本分子生物学会, 横浜, Domestic conference

  Oral presentation


• DNA損傷認識を制御するクロマチン構造動態

  KAKUMU ERINA, 中西 正哉, SAKAI WATARU, ADACHI NAOKO, SAITO NAOAKI, 森 俊雄, 木村 宏, 胡桃坂 仁志, SUGASAWA KAORU

  第39回日本分子生物学会年会（MBSJ2016）, Nov. 2016, Japanese, 日本分子生物学会, 横浜, Domestic conference

  Poster presentation


• ヌクレオチド除去修復のDNA損傷認識とその制御の分子基盤

  SUGASAWA KAORU, HARUTO TADA, 大西 優貴, 岩井成憲, 胡桃坂仁志, SAKAI WATARU

  第89回日本生化学会大会, Sep. 2016, Japanese, 日本分子生物学会, 仙台, Domestic conference

  Oral presentation


• Dynamics of chromatin structure regulating nucleotide excision repair

  Erina Kakumu, Seiya Nakanishi, Wataru Sakai, Naoko Adachi, Naoaki Saito, Hiroshi Kimura, Kaoru Sugasawa

  Conference on Responses to DNA Damage: from Molecule to Disease, Apr. 2016, English, Egmond aan Zee, The Netherlands, International conference

  Poster presentation


• ヌクレオチド除去修復を制御するクロマチン構造動態の解析

  各務 恵理菜, 中西 正哉, 酒井 恒, ADACHI NAOKO, SAITO NAOAKI, 田嶋 正二, 菅澤 薫

  第38回日本分子生物学会年会・第88回日本生化学会大会合同大会(BMB2015), Dec. 2015, Japanese, 日本分子生物学会, 神戸, Domestic conference

  Poster presentation


• タンパク質分解系による紫外線損傷応答制御

  酒井 恒, 岸本 藍子, 松井 豪志, 金子 雄貴, 赤木 純一, 菅澤 薫

  第38回日本分子生物学会年会・第88回日本生化学会大会合同大会(BMB2015), Dec. 2015, Japanese, 日本分子生物学会, 神戸, Domestic conference

  Oral presentation


• ゲノム損傷応答におけるp53とDDB2の機能連関

  上村 美花, 松本 翔太, 安田 武嗣, 酒井 恒, 菅澤 薫

  第38回日本分子生物学会年会・第88回日本生化学会大会合同大会(BMB2015), Dec. 2015, Japanese, 日本分子生物学会, 神戸, Domestic conference

  Poster presentation


• ユビキチンープロテアソーム系による紫外線誘発DNA損傷応答制御

  酒井 恒, 金子 雄貴, 岸本 藍子, 松井 豪志, 赤木 純一, 菅澤 薫

  第23回DNA複製・組換え・修復ワークショップ, Oct. 2015, Japanese, DNA複製・組換え・修復ワークショップ研究会, 焼津, Domestic conference

  Oral presentation


• 紫外線損傷修復におけるXPCタンパク質の脱ユビキチン化制御機構の解析

  酒井 恒, 岸本 藍子, 松井 豪志, 赤木 純一, 菅澤 薫

  日本遺伝学会第87回大会, Sep. 2015, Japanese, 日本遺伝学会, 仙台, Domestic conference

  Oral presentation


• Molecular mechanism of DNA damage recognition in mammalian nucleotide excision repair.

  Onishi Y, Tone D, Kinoshita M, Iwai S, Sakai W, Sugasawa, K

  15th International Congress of Radiation Research, May 2015, English, ICRR, 京都, International conference

  Oral presentation


• ヌクレオチド除去修復の制御に関わるクロマチン構造動態

  中西 正哉, 各務 恵理菜, 酒井 恒, SUGASAWA KAORU

  日本薬学会第135年会, Mar. 2015, Japanese, 神戸学院大学, Domestic conference

  Oral presentation


• 翻訳後修飾を介した色素性乾皮症遺伝子産物の機能制御

  秋田 眞季, 松本 翔太, 井倉 毅, 酒井 恒, SUGASAWA KAORU

  第37回日本分子生物学会年会, Nov. 2014, Japanese, パシフィコ横浜, Domestic conference

  Oral presentation


• ゲノム損傷応答におけるGadd45αの機能解析

  小山 紗季, 北野 健太, INASE AKI, 酒井 恒, 菅澤 薫

  第37回日本分子生物学会年会, Nov. 2014, Japanese, パシフィコ横浜, Domestic conference

  Poster presentation


• Studies on the de-ubiquitination mechanism of the xeroderma pigmentosum group C protein

  Kishimoto, A, Akagi, J, Matsui, T, Matsumoto, S, Sakai, W, Sugasawa, K

  The 9th 3R Symposium Together with National Instituite of Genetics 2014 International Symposium, Nov. 2014, English, 御殿場高原ホテル, International conference

  Poster presentation


• DNA損傷応答におけるDDB2の翻訳後修飾の機能解析

  松本 翔太, Fischer, E. S, Thomä, N. H, 酒井 恒, 菅澤 薫

  第37回日本分子生物学会年会, Nov. 2014, Japanese, パシフィコ横浜, Domestic conference

  Poster presentation


• DNA修復・損傷応答におけるクロマチン構造ダイナミクスの解析

  各務 恵理菜, 中西 正哉, 酒井 恒, 木村 宏, 菅澤 薫

  第37回日本分子生物学会年会, Nov. 2014, Japanese, パシフィコ横浜, Domestic conference

  Poster presentation


• 紫外線損傷修復におけるXPCタンパク質の脱ユビキチン化機構の解析

  岸本 藍子, 赤木 純一, 松井 豪志, 酒井 恒, 菅澤 薫

  日本遺伝学会第86回大会, Sep. 2014, Japanese, 長浜バイオ大学, Domestic conference

  Poster presentation


• Roles for post-translational protein modifications in regulation of DNA damage recognition for mammalian nucleotide excision repair

  Akita, M, Matsumoto, S, Sakai,W, Sugasawa,K

  International Symposium on Xeroderma Pigmentosum and Related Diseases, Mar. 2014, English, Kobe, Japan, International conference

  Oral presentation


• Molecular analysis of DNA repair defects in cells from Japanese patients with xeroderma pigmentosum Group D

  Mayca Pozo, F, Sakai,W, van der Spek, P. J, Nakazawa, Y, Ogi, T, Ono, R, Nishigori, C, Sugasawa,K

  International Symposium on Xeroderma Pigmentosum and Related Diseases, Mar. 2014, English, Kobe, Japan, International conference

  Poster presentation


• A child case of xeroderma pigmentosum group D.

  R Ono, T Masaki, E Nakano, FM Pozo, Sakai Wataru, PJ van der Spek, S Takeuchi, T Ogi, Sugasawa Kaoru, C Nishigori

  International Symposium on Xeroderma Pigmentosum and related diseases, Mar. 2014, English, Kobe, International conference

  Poster presentation


• ヌクレオチド除去修復の損傷認識に関わるクロマチン構造制御

  中西 正哉, 酒井 恒, 白鳥 広海, 木村 宏, 菅澤 薫

  第36回日本分子生物学会年会, Dec. 2013, Japanese, 神戸, Domestic conference

  Poster presentation


• FANCD2タンパク質はアポトーシスを抑制的に制御する

  SAKAI WATARU, SUGASAWA KAORU

  第36回日本分子生物学会年会, Dec. 2013, Japanese, 神戸, Domestic conference

  Oral presentation


• DNA修復異常を伴う光線過敏症患者の分子細胞生物学的解析

  酒井 恒, Franklin Mayca Pozo, 菅澤 薫, 中沢 由華, 荻 朋男, 小野 竜輔, 錦織 千佳子

  厚生労働省科学研究費「神経皮膚症候群に関する調査研究班」平成25年度総会, Dec. 2013, Japanese, 神経皮膚症候群に関する調査研究班, 東京, Domestic conference

  Others


• ファンコニ貧血症タンパク質FANCD2によるアポトーシス制御機構

  SAKAI WATARU, SUGASAWA KAORU

  第31回染色体ワークショップ・第12回核ダイナミクス研究会, Nov. 2013, Japanese, 箱根, Domestic conference

  Oral presentation


• ファンコニ貧血症タンパク質FANCD2によるアポトーシス制御機構

  SAKAI WATARU, SUGASAWA KAORU

  第22回DNA複製・組換え・修復ワークショップ, Nov. 2013, Japanese, 仙台, Domestic conference

  Poster presentation


• Functional interactions of DNA damage repair with transcriptional and epigenetic regulation

  Matsumoto, S, Nakanishi, S, Sakai,W, Sugasawa,K

  International Symposium on Transcription and Metabolism, Nov. 2013, English, Awaji, Japan, International conference

  Oral presentation


• Chromatin structure regulating DNA damage recognition in nucleotide excision repair

  Nakanishi, S, Sakai,W, Shiratori, H, Kimura, H, Sugasawa,K

  International Symposium on Transcription and Metabolism, Nov. 2013, English, Awaji, Japan, International conference

  Oral presentation


• 紫外線誘発DNA損傷の修復機構におけるSUMO化修飾の役割

  AKITA MASAKI, SAKAI WATARU, SUGASAWA KAORU

  日本放射線影響学会第56回大会, Oct. 2013, Japanese, 青森, Domestic conference

  Oral presentation


• FANCD2 in chromatin anchors CtIP and regulates DNA end resection during crosslink repair.

  Unno J, Itaya A, Taoka M, Sato K, Tomida J, Sakai Wataru, Ikura T, Isobe T, Kurumizaka H, Takata M

  25th Annual Fanconi Anemia Research Fund Scientific Symposium, Oct. 2013, English, Houston, Texas, International conference

  Oral presentation


• FANCD2はDNA修復に関わる機能とは独立してTNFα/TNFR1を介したアポトーシス機構を負に制御している

  SAKAI WATARU, SUGASAWA KAORU

  第22回日本Cell Death学会学術集会, Jul. 2013, Japanese, 京都, Domestic conference

  Oral presentation


• FANCD2遺伝子産物はDNA修復とは独立したアポトーシス抑制機能を有する

  SAKAI WATARU, SUGASAWA KAORU

  日本遺伝学会第85回大会, 2013, Japanese, 横浜, Domestic conference

  Oral presentation


• FANCD2 タンパク質はアポトーシスを抑制的に制御する

  酒井 恒, 菅澤 薫

  第30回染色体ワークショップ, Dec. 2012, Japanese, 淡路, Domestic conference

  Public symposium


• A novel function of FANCD2 protein in apoptosis signaling (2ST2-026)

  Sakai, W, Sugasawa,K

  第35回日本分子生物学会年会, Dec. 2012, Japanese, 日本分子生物学会, 福岡, Domestic conference

  Poster presentation


• A novel function of centrin-2 involved in maintenance of genomic stability.

  SUGASAWA KAORU, Nishi,R, SAKAI WATARU, TONE DAISUKE, Hanaoka,F

  第35回日本分子生物学会, Dec. 2012, Japanese, 福岡, Domestic conference

  Oral presentation


• Genotoxic stress induces caspase-mediated cleavage of the FANCD2 protein.

  Sakai,W, Sugasawa,K

  The 8th 3R Symposium (International Symposium on DNA Replication, Recombination and Repair), Nov. 2012, English, Awaji, International conference

  Public symposium


• DNA repair synthesis defect in xeroderma pigmentosum group D cells.

  Mayca Pozo, F, Sakai, W, Peter J. van, der Spek, Nakazawa,Y, Ogi, T, Nishigori,C, Sugasawa,K

  The 8th 3R Symposium (International Symposium on DNA Replication, Recombination and Repair), Nov. 2012, English, Awaji, International conference

  Public symposium


• 紫外線損傷修復におけるXPCタンパク質の脱ユビキチン化機構の解析

  赤木 純一, 松井 豪志, SAKAI WATARU, SUGASAWA KAORU

  日本遺伝学会第84回大会, Sep. 2012, Japanese, 福岡, Domestic conference

  Oral presentation


• DNA損傷ストレスに伴うFANCD2タンパク質のカスパーゼ依存的切断

  酒井 恒, 菅澤 薫

  第29回染色体ワークショップ, Jan. 2012, Japanese, 仙台, Domestic conference

  Oral presentation


• Genotoxic stress induces caspase-mediated cleavage of the FANCD2 protein

  Wataru Sakai, Kaoru Sugasawa

  第34回日本分子生物学会年会, Dec. 2011, Japanese, 日本分子生物学会, 横浜, Domestic conference

  Oral presentation


• DNA損傷ストレスに伴うFANCD2タンパク質のカスパーゼ依存的切断

  Wataru Sakai, Kaoru Sugasawa

  第33回日本分子生物学会年会・第83回日本生化学会大会合同大会, Dec. 2010, Japanese, 日本分子生物学会, 神戸ポートアイランド, Domestic conference

  Oral presentation


• Roles for centrin-2 in DNA damage recognition for global genome nucleotide excision repair

  Kaoru Sugasawa, Ryotaro Nishi, Yon-Soo Tak, Wataru Sakai, Fumio Hanaoka

  The 7th 3R Symposium (International Symposium on DNA Replication, Recombination and Repair), Oct. 2010, English, 第7回3Rシンポジウム実行委員会, 富山国際会議場, Domestic conference

  Oral presentation


• Genotoxic stress induces caspase-mediated cleavage of the FANCD2 protein

  Kaoru Sugasawa, Wataru Sakai

  The 7th 3R Symposium (International Symposium on DNA Replication, Recombination and Repair), Oct. 2010, English, 第7回3Rシンポジウム実行委員会, 富山, Domestic conference

  Poster presentation


• Genotoxic stress targets Fanconi anemia group D2 protein for fragmentation by the caspase-mediated pathway

  Sakai Wataru, Sugasawa Kaoru

  第32回日本分子生物学会年会, Dec. 2009, Japanese, 日本分子生物学会, パシフィコ横浜, Domestic conference

  Poster presentation


• DNA損傷に伴うFANCD2(FA-D2)タンパク質のcaspase依存的切断

  Sakai Wataru, Sugasawa Kaoru

  日本遺伝学会第81回大会, Sep. 2009, Japanese, 日本遺伝学会, 松本, Domestic conference

  Oral presentation


• BRCA2変異卵巣癌細胞における第二のBRCA2変異は機能的BRCA2を復活させ、抗癌剤に対する耐性の原因となる

  Sakai Wataru

  BMB2008 第31回日本分子生物学会年会・第81回日本生化学会大会, Dec. 2008, Japanese, Kobe, Domestic conference

  Oral presentation


• BRCA2変異卵巣癌細胞における第二のBRCA2変異は機能的BRCA2を復活させ、抗癌剤に対する耐性の原因となる

  Sakai Wataru

  国立遺伝学研究所研究集会「ユビキチン・SUMOによるDNA複製およびDNA修復系の制御」, Oct. 2008, Japanese, 三島, Domestic conference

  Oral presentation

• ファンコニ貧血における脂肪族アルデヒド代謝の影響

  酒井 恒

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2020 - 31 Mar. 2023

  申請者はファンコニ貧血の責任遺伝子産物（FAタンパク質）の1つであるFANCD2タンパク質と脂質代謝に関与する酵素の1つが相互作用することを質量分析によって見出した。当該年度においては、免疫沈降等により、それらの相互作用が外部からのDNA損傷ストレスに依存せず比較的安定的であることが明らかとなった。また、前年度に樹立した脂質代謝関連遺伝子のノックアウト細胞株を用いて、その影響について解析を行なった。具体的には、1）脂質代謝因子のノックアウトによって細胞増殖に遅延が見られたが、2）DNA損傷に応答したFANCD2のモノユビキチン化には異常は見られなかった。しかし、3）ヒストンバリアントH2AXのリン酸化（DNA損傷マーカーとして知られる）の顕著な減弱が見出された。本研究課題で着目している脂質代謝関連因子はDNA損傷応答・修復への関与は全く報告されておらず、特に3）の結果は脂質代謝制御とDNA損傷のシグナル伝達の新たな機能的連関を示唆する成果と言える。今後より詳細にこれらのシグナル伝達経路を解析するため、樹立したノックアウト細胞に野生型、または変異導入によって酵素活性を欠失した変異型を安定発現した細胞をすでに樹立済みである。 また、申請者はFANCD2遺伝子のノックアウトによって脂質代謝制御に異常が見られることを前年度に明らかにしたが、同様の脂質代謝異常が他のFAタンパク質の発現抑制によっても引き起こされることが新たに判明した。これらの結果はFANCD2のみならず、他のFAタンパク質においても脂質代謝制御に関与する可能性を示唆しており、ファンコニ貧血患者において見られる脂質代謝異常の病態との関連性が期待される。


• ファンコニ貧血タンパク質とアルデヒド代謝の新たな相互制御関係の解明

  酒井 恒

  学術研究助成基金助成金／基盤研究(C), Apr. 2017 - Mar. 2020, Principal investigator

  Competitive research funding


• Cross-regulation of the maintenance and mutagenesis of genomic sequence and epigenetic information

  Sugasawa Kaoru, SAKAI Wataru, IWAI Shigenori, INASE Aki, MATSUMOTO Syota, TONE Daisuke, NAKAMURA Tomohumi, NAKANISHI Seiya, KAKUMU Erina, KOYAMA Saki, Kishimoto Aiko, UEMURA Mika, KANEKO Yuki, GOTO Motonari

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Kobe University, 01 Apr. 2011 - 31 Mar. 2016

  In this study, it is suggested that formation of heterochromatin-like structures is involved in regulation of intracellular localization of DNA damage recognition factors for nucleotide excision repair. We also elucidate novel roles of various post-translational modifications (ubiquitination, SUMOylation, acetylation, etc.) in functional regulation of the DDB2 protein, which is involved in crosstalks between DNA repair and transcription, thereby regulating cellular DNA damage responses. Furthermore, the molecular mechanism is uncovered for regulating stability of thymine DNA glycosylase (TDG), which is a key factor involved in both base excision repair suppressing spontaneous mutagenesis as well as active DNA demethylation. TDG is also shown to interact functionally with the nucleotide excision repair pathway by affecting functions of the xeroderma pigmentosum group C (XPC) protein.


• ファンコニ貧血症タンパク質によるアポトーシス制御に関わる新たな分子機構の解明

  酒井 恒

  学術研究助成基金助成金／若手研究(B), Apr. 2014 - Mar. 2016, Principal investigator

  Competitive research funding


• Analysis of a novel molecular mechanism for decision of cell fate in response to DNA damage

  SAKAI Wataru

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (A), Kobe University, 2010 - 2012, Principal investigator

  FANCD2is one ofthe responsiblegenes for a rare genetic disorder, Fanconi anemia syndrome. Many researchers reported that FANCD2 protein is a key factor for DNA interstrand crosslink repair. In the pilot study, I found a novel phenomenon that the FANCD2 protein was cleaved into atleast four smaller fragments when cells were treated with relatively high doses of genotoxic agents. In vitro and in vivo analyses showed that the DNA damage-induced cleavage of FANCD2 was dependent on caspase-3. All the cleavage sites were identified and the mutant FANCD2 protein lacking those cleavage sites was generated. When the non-cleavable mutant FANCD2 protein was stably expressed in a FANCD2-deficient cell line, the cells showed resistance to genotoxic agents compared with the cell line expressed wild-type FANCD2 protein. In the absence of exogenous genotoxic stress, however, only cell line expressed wild-type FANCD2 showed significant resistance to apoptosis induction by caspase-8 activation. All these results implied the possibility that FANCD2 contributes to regulate apoptosis induction negatively independent of DNA repair response.

  Competitive research funding