Regulation of translesion DNA synthesis by post-translational modifications

• Project/Area Number: 19310036
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Osaka University
• Principal Investigator: MASUTANI Chikahide Osaka University, 大学院・生命機能研究科, 准教授 (40241252)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000); Fiscal Year 2009: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 損傷乗り越えDNA複製 / DNA複製 / 翻訳後修飾 / POLH / PCNA / ユビキチン化 / リン酸化 / DNAポリメラーゼ・イータ / 損傷乗り越え複製 / Polη

Research Abstract

Human DNA polymerase eta (Polη) is the responsible gene product of xeroderma pigmentosum variant, a cancer-prone genetic disorder, and protects cells from cell death or carcinogenesis by catalyzing accurate translesion DNA synthesis (TLS). During this project, we showed that Polη has mutagenic properties depending on DNA damages and situations. We have also identified novel protein-protein interactions and post-translational modifications of Polη and related proteins which could be important for regulating TLS in human cells.

Research Products

• [Journal Article] The molecular chaperone Hsp90 regulates accumulation of DNA polymerase η at replication stalling sites in UV-irradiated cells (2010)
  • Author(s): Sekimoto, T., Oda, T., Pozo, F.M., Murakumo, Y., Masutani, C., Hanaoka, F., Yamashita, T
  • Journal Title: Mol. Cell 37 Pages: 79-89
  • Peer Reviewed
• [Journal Article] Polymerization by DNA polymerase η is blocked by cis-diamminedichloroplatinum(II) 1, 3-d(GpTpG) crosslink: Implications for cytotoxic effects in nucleotide excision repair-negative tumor cells (2010)
  • Author(s): Chijiwa, S., Masutani, C., Hanaoka, F., Iwai, S., Kuraoka, I
  • Journal Title: Carcinogenesis 31 Pages: 388-393
  • Peer Reviewed
• [Journal Article] Critical amino acids involved in erroneous incorporation of oxidized nucleotides by human DNA polymerase η and κ (2010)
  • Author(s): Katafuchi, A., Sassa, A., Niimi, N., Gruz, P., Fujimoto, H., Masutani, C., Hanaoka, F., Ohta, T., Nohmi, T
  • Journal Title: Nucleic Acids Res 38 Pages: 859-867
  • Peer Reviewed
• [Journal Article] The molecular chaperone Hsp90 regulates accumulation of DNA polymerase η at replication stalling sites in UV-irradiated cells. (2010)
  • Author(s): Sekimoto, et al.
  • Journal Title: Mol.Cell 37 Pages: 79-89
  • Peer Reviewed
• [Journal Article] Polymerization by DNA polymerase η is blocked by cis-diamminedichloroplatinum(II) 1,3-d(GpTpG) crosslink : Implications for cytotoxic effects in nucleotide excision repair-negative tumor cells. (2010)
  • Author(s): Chijiwa, et al.
  • Journal Title: Carcinogenesis 31 Pages: 388-393
  • Peer Reviewed
• [Journal Article] Critical amino acids involved in erroneous incoration of oxidized nucleotides by human DNA polymerase η and κ. (2010)
  • Author(s): Katafuchi, et al.
  • Journal Title: Nucl.Acids Res. 38 Pages: 589-867
  • Peer Reviewed
• [Journal Article] The molecular chaperone Hsp90 regulates accumulation of DNA polymerase η at replication stalling sites in UV-irradiated cells (2010)
  • Author(s): Sekimoto, et al.
  • Journal Title: Mol.Cell 37 Pages: 79-89
  • Peer Reviewed
• [Journal Article] Polymerization by DNA polymerase η is blocked by cis-diamminedichloroplatinum(II)1,3-d(GpTpG)crosslink : Implications for cytotoxic effects in nucleotide excision repair-negative tumor cells (2010)
  • Author(s): Chijiwa, et al.
  • Journal Title: Carcinogenesis 31 Pages: 388-393
  • Peer Reviewed
• [Journal Article] Critical amino acids involved in erroneous incorporation of oxidized nucleotides by human DNA polymerase η and κ (2010)
  • Author(s): Katafuchi, et al.
  • Journal Title: Nucl.Acids Res. 38 Pages: 859-867
  • Peer Reviewed
• [Journal Article] A novel interaction between human DNA polymerase η and MutLα (2009)
  • Author(s): Kanao, R., Hanaoka, F., Masutani, C
  • Journal Title: Biochem. Biophys. Res. Commun 389 Pages: 40-45
  • Peer Reviewed
• [Journal Article] Translesional DNA synthesis through a C8-guanyl adduct of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) in vitro: REV1 inserts dC opposite the lesion and DNA polymerase κ potentially catalyzes extension reaction from the 3'-dC terminus (2009)
  • Author(s): Fukuda, H., Takamura-Enya, T., Masuda, Y., Nohmi, T., Seki, C., Kamiya, K., Sugimura, T., Masutani, C., Hanaoka, F., Nakagama, H
  • Journal Title: J. Biol. Chem 284 Pages: 25585-25592
  • Peer Reviewed
• [Journal Article] Interaction with DNA polymerase η is required for nuclear accumulation of REV1 and suppression of spontaneous mutations in human cells (2009)
  • Author(s): Akagi, J., Masutani, C., Kataoka, Y., Kan, T., Ohashi, E., Mori, T., Ohmori, H., Hanaoka, F
  • Journal Title: DNA Repair 8 Pages: 585-599
  • Peer Reviewed
• [Journal Article] Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases (2009)
  • Author(s): Kimura, T., Takeuchi, T., Kumamoto-Yonezawa, Y., Ohashi, E., Ohmori, H., Masutani, C., Hanaoka, F., Sugawara, F., Yoshida, H., Mizushina, Y
  • Journal Title: Bioorganic Medicinal Chemistry 17 Pages: 1811-1816
  • Peer Reviewed
• [Journal Article] A novel interaction between human DNA polymerase η and MutLα. (2009)
  • Author(s): Kanao, et al .
  • Journal Title: Biochem.Biophys.Res.Commun. 389 Pages: 40-45
  • Peer Reviewed
• [Journal Article] Translesional DNA synthesis through a C8-guanyl adduct of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine(PhIP)in vitro. REV1 inserts dC opposite the lesion and DNA polymerase κ potentially catalyzes extension reaction from the 3'-dC terminus. (2009)
  • Author(s): Fukuda, et al.
  • Journal Title: J.Biol.Chem. 284 Pages: 25585-25592
  • Peer Reviewed
• [Journal Article] Interaction with DNA polymerase η is required for nuclear accumulation of REV1 and suppression of spontaneous mutations in human cells. (2009)
  • Author(s): Akagi, et al.
  • Journal Title: DNA Repair 8 Pages: 585-599
  • Peer Reviewed
• [Journal Article] Interaction with DNA polymerase η is required for nuclear accumulation of REV1 and suppression of spontaneous mutations in human cells (2009)
  • Author(s): Akagi, J., et al.
  • Journal Title: DNA Repair(Amst.) Pages: 585-599
  • Peer Reviewed
• [Journal Article] Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerasaes (2009)
  • Author(s): Kimura, T., et al.
  • Journal Title: Bioorg.Med.Chem. 17 Pages: 1811-1816
  • Peer Reviewed
• [Journal Article] A novel interaction between human DNA polymerase η and MutLα (2009)
  • Author(s): Kanao, et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 389 Pages: 40-45
  • Peer Reviewed
• [Journal Article] Translesional DNA synthesis through a C8-guanyl adduct of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine(PhIP)in vitro : REV1 inserts dC opposite the lesion and DNA polymerase κ potentially catalyzes extension reaction from the 3'-dC terminus (2009)
  • Author(s): Fukuda, et al.
  • Journal Title: J.Biol.Chem. 284 Pages: 25585-25592
  • Peer Reviewed
• [Journal Article] Miscoding property of 2'-deoxyinosine, a nitric oxide-derived DNA adduct, during translesion synthesis catalyzed by human DNA polymerases (2008)
  • Author(s): Yasui, M., Suenaga, E., Koyama, N., Masutani, C., Hanaoka, F., Gruz, P., Shibutani, S., Nohmi, T., Hayashi, M., Honma, M
  • Journal Title: J. Mol. Biol 377 Pages: 1015-1023
  • Peer Reviewed
• [Journal Article] Specificity of mutations induced by incorporation of oxidized dNTPs into DNA by human DNA polymeraseη (2008)
  • Author(s): Hidaka, K., Yamada, M., Kamiya, H., Masutani, C., Harashima, H., Hanaoka, F., Nohmi, T
  • Journal Title: DNA Repair 7 Pages: 497-506
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): Masutani, C., et al.
  • Journal Title: Xeroderma pigmentosum variant, XP-V : its product and biological roles.In Molecular Mechanisms of Xeroderma Pigmentosum(Landes Bioscience) Pages: 93-102
• [Journal Article] (2008)
  • Author(s): Ohkumo, T., et al.
  • Journal Title: Use of RNAi in C.elegans.In Methods Mol.Biol(Springer Link) Pages: 129-137
• [Journal Article] Miscoding property of 2'-deoxyinosine, a nitric oxide-derived DNA adduct, during translesion synthesis catalyzed by human DNA polymerases. (2008)
  • Author(s): Yasui, M., et. al.
  • Journal Title: J. Mol. Biol (in press)
  • Peer Reviewed
• [Journal Article] Specificity of mutations induced by incorporation of oxidized dNTPs into DNA by human DNA polymerase η. (2008)
  • Author(s): Hidaka, K.., et. al.
  • Journal Title: DNA Repair (Amst} 7 Pages: 497-506
  • Peer Reviewed
• [Journal Article] A second PCNA loader complex, Ctf18-RFC, specifically stimulates DNA polymerase η activity (2007)
  • Author(s): Shiomi, Y., Masutani, C., Hanaoka, F., Kimura, H., Tsurimoto, T
  • Journal Title: J. Biol. Chem 282 Pages: 20906-20914
  • Peer Reviewed
• [Journal Article] 2-Hydroxy-2'-deoxyadenosine 5'-triphosphate enhances A. T-> C. G mutations caused by 8-hydroxy-2'-deoxyguanosine 5'-triphosphate by suppressing its degradation upon replication in a HeLa extract (2007)
  • Author(s): Satou, K., Kasai, H., Masutani, C., Hanaoka, F., Harashima, H., Kamiya, H
  • Journal Title: Biochemistry 46 Pages: 6639-6646
  • Peer Reviewed
• [Journal Article] DNA polymerase η and θ function in the same genetic pathway to generate mutations at A/T during somatic hypermutation of Ig genes (2007)
  • Author(s): Masuda, K., Ouchida, R., Hikida, M., Kurosaki, T., Yokoi, M., Masutani, C., Seki, M., Wood, R.D., Hanaoka, F., O-Wang, J
  • Journal Title: J. Biol. Chem 282 Pages: 17387-17394
  • Peer Reviewed
• [Journal Article] Efficient and erroneous incorporation of oxidized DNA precursors by human DNA polymerase η (2007)
  • Author(s): Shimizu, M., Gruz, P., Kamiya, H., Masutani, C., Xu, Y., Sugiyama, H., Harashima, H., Hanaoka, F., Nohmi, T
  • Journal Title: Biochemistry 46 Pages: 5515-5522
  • Peer Reviewed
• [Journal Article] A second PCNA loader complex, Ctf18-RFC, specifically stimulates DNA polymerase η activity. (2007)
  • Author(s): Shiomi, Y., et. al.
  • Journal Title: J. Biol. Chem. 282 Pages: 20906-20914
  • Peer Reviewed
• [Journal Article] 2-Hydroxy-2'-deoxyadenosine 5'-triphosphate enhances A. T-> C. G mutations caused by 8-hydroxy-2'-deoxygu anosine 5'-triphosphate by suppressing its degradation upon replication in a HeLa extract. (2007)
  • Author(s): Satou, K., et. al.
  • Journal Title: Biochemistry 46 Pages: 6639-6646
  • Peer Reviewed
• [Journal Article] DNA polymerase η and θ function in the same genetic pathway to generatemutations at A/T during somatic hypermutation of Ig genes. (2007)
  • Author(s): Masuda, K,. et. al.
  • Journal Title: J. Biol. Chem. 282 Pages: 17387-17394
  • Peer Reviewed
• [Journal Article] Efficient and erroneous incorporation of oxidized DNA precursors by human DNA polymerase η. (2007)
  • Author(s): Shimizu, M., et. al.
  • Journal Title: Biochemistry 46 Pages: 5515-5522
  • Peer Reviewed
• [Presentation] Analysis of regulatory mechanisms of human pol eta, the XPV gene product (2009)
  • Author(s): 益谷央豪
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Physiological relevance of post-translational modifications of PCNA at lysine-164 in human cells (2009)
  • Author(s): 金尾梨絵、出口沙織、湯本真弓、花岡文雄、益谷央豪
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] The molecular chaperone Hsp90 promotes DNA damage-induced nuclear focus formation of Y-family DNA polymerase REV1 (2009)
  • Author(s): Franklin Mayca Pozo、小野司、関本隆志、益谷央豪、花岡文雄、村雲芳樹、山下孝之
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Human REV1 is phosphorylated and accumulated at spindle poles in mitotic cells (2009)
  • Author(s): 赤木純一、片岡裕貴、益谷央豪、花岡文雄
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases (2009)
  • Author(s): 水品善之、木村拓馬、竹内倫文、米澤裕子、大橋英治、大森治夫、益谷央豪、花岡文雄、吉田弘美、菅原二三男、坂口健吾
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Analysis of regulatory mechanisms of human pol eta, the XPV gene product. (2009)
  • Author(s): 益谷央豪
  • Organizer: 第32回日本分子生物学会年会 ワークショップ
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Physiological relevance of post-translational modifications of PCNA at lysine-164 in human cells. (2009)
  • Author(s): 金尾梨絵, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] The molecular chaperone Hsp90 promotes DNA damage-induced nuclear focus formation of Y-family DNA polymerase REV1. (2009)
  • Author(s): Franklin Mayca Pozo, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Human REV1 is phosphorylated and accumulated at spindle poles in mitotic cells. (2009)
  • Author(s): 赤木純一, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Penicilliols A and B, novel inhibitors specific to mammalian Y-famliy DNA polymerases (2009)
  • Author(s): 水品善之
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Analysis of regulatory mechanisms of human pol eta, the XPV gene product (2009)
  • Author(s): 益谷央豪
  • Organizer: 第32回日本分子生物学会年会 ワークショップ
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] The molecular chaperone Hsp90 promotes DNA damage-induced nuclear focus formation of Y-family DNA nolymerase REV1 (2009)
  • Author(s): Franklin Mayca Pozo, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] 蛋白質間相互作用と翻訳後修飾による損傷乗り越えDNA複製の制御 (2008)
  • Author(s): 益谷央豪
  • Organizer: 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
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 蛋白質間相互作用と翻訳後修飾による損傷乗り越えDNA複製の制御 (2008)
  • Author(s): 益谷央豪
  • Organizer: BMB2008シンポジウム「ゲノムの安定性と多様化を制御する分子機構」
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 損傷乗り越えDNA複製におけるタンパク質間相互作用 (2008)
  • Author(s): 益谷央豪、花岡文雄
  • Organizer: 第67回日本癌学会学術総会シンポジウム
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-29
• [Presentation] 損傷乗り越えDNA複製におけるタンパク質間相互作用 (2008)
  • Author(s): 益谷央豪、花岡文雄
  • Organizer: 第67回日本癌学会学術総会シンポジウム「DNA修復ネットワークの異常と発癌」
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] DNAポリメラーゼηのリン酸化による機能制御の解析 (2008)
  • Author(s): 小野香苗、花岡文雄、益谷央豪
  • Organizer: 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合同大会)
  • Place of Presentation: 神戸
• [Presentation] PCNAのモノユビキチン化を制御するメカニズムの探索 (2008)
  • Author(s): 徐菲、花岡文雄、益谷央豪
  • Organizer: 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合同大会)
  • Place of Presentation: 神戸
• [Presentation] Physiological relevance of the Pol eta-REV1 interaction in human cells (2008)
  • Author(s): Masutani, C., Akagi, J., Kataoka, Y., Ohashi, E., Iwai, S., Ohmori, H., Hanaoka, F
  • Organizer: International Symposium on Chromosome Dynamics in Ise
  • Place of Presentation: Toba, Japan
• [Presentation] Physiological relevance of the Pol eta-Rev1 interaction in human cells (2008)
  • Author(s): Masutani, C., Akagi, J., Kataoka, Y., Ohashi, E., Iwai, S., Ohmori, H., Hanaoka, F
  • Organizer: The International Ataxia-telangiectasia Workshop 2008 (ATW2008)
  • Place of Presentation: Ohtsu, Japan
• [Presentation] Physiological relevance of the Pol eta-Revl interaction in human cells (2008)
  • Author(s): 益谷央豪, et al.
  • Organizer: 3R symposium
  • Place of Presentation: 嬬恋
• [Presentation] UV-induced mutagenesis in skin genome from DNA polymerase eta and iota deficient mice (2008)
  • Author(s): 金尾梨絵, et al.
  • Organizer: 3R symposium
  • Place of Presentation: 嬬恋
• [Presentation] Physiological relevance of the Pol eta-Revl interaction in human cells (2008)
  • Author(s): 益谷央豪, et al.
  • Organizer: International Symposium on Chromosome Dynamics in Ise
  • Place of Presentation: 鳥羽
• [Presentation] Analysis of the interaction between human DNA polymerase eta and mismatch repair proteins (2008)
  • Author(s): 金尾梨絵, et al.
  • Organizer: International Symposium on Chromosome Dynamics in Ise
  • Place of Presentation: 鳥羽
• [Presentation] Physiological relevance of the Pol eta-Revl interaction in human cells (2008)
  • Author(s): 益谷央豪, et al.
  • Organizer: Ataxia-telangiectasia Workshop 2008
  • Place of Presentation: 大津
• [Presentation] DNAポリメラーゼη及びν欠損マウスの皮膚における紫外線誘発突然変異の解析 (2008)
  • Author(s): 金尾梨絵, 他
  • Organizer: 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合同大会)
  • Place of Presentation: 神戸
• [Presentation] 損傷乗り越え複製の分子機構-DNAポリメラーゼ・イータを中心に- (2007)
  • Author(s): 花岡文雄、他
  • Organizer: BMB2007(第30回日本分子生物学会年会 第80回日本生化学会大会 合同大会)
  • Place of Presentation: 横浜
• [Presentation] Do UV-inducible DNA damages produce chickenfoot intermediates in the in vitro DNA replication system with human cell-free extracts? (2007)
  • Author(s): 菅野 毅治、他
  • Organizer: BMB2007(第30回日本分子生物学会年会 第80回日本生化学会大会 合同大会)
  • Place of Presentation: 横浜
• [Presentation] Analysis of interaction between DNA polymerase eta and Fanconi anemia proteins (2007)
  • Author(s): 小野 香苗、他
  • Organizer: BMB2007(第30回日本分子生物学会年会 第80回日本生化学会大会 合同大会)
  • Place of Presentation: 横浜
• [Presentation] DNAポリメラーゼηとミスマッチ修復因子の相互作用の解析 (2007)
  • Author(s): 金尾 梨絵、他
  • Organizer: BMB2007(第30回日本分子生物学会年会 第80回日本生化学会大会 合同大会)
  • Place of Presentation: 横浜
• [Presentation] PCNAのモノユビキチン化を制御する因子の探索 (2007)
  • Author(s): Fei Xu、他
  • Organizer: BMB2007(第30回日本分子生物学会年会 第80回日本生化学会大会 合同大会)
  • Place of Presentation: 横浜
• [Presentation] ヒト細胞におけるPCNA K164の翻訳後修飾(ユビキチン化?)の生理的意義の解析 (2007)
  • Author(s): 出口 沙織、他
  • Organizer: BMB2007(第30回日本分子生物学会年会 第80回日本生化学会大会 合同大会)
  • Place of Presentation: 横浜
• [Presentation] 分子シャペロンHsp90はTranslesion DNA Synthesis(TLS)に関与するDNA polymerase-eta(Pol-η)のReplication focus(RF)への動員に必要である (2007)
  • Author(s): 関本 隆志、他
  • Organizer: BMB2007(第30回日本分子生物学会年会 第80回日本生化学会大会 合同大会)
  • Place of Presentation: 横浜
• [Book] Xeroderma Pigmentosum Variant, XP-V: its product and biological roles (2008)
  • Author(s): Masutani, C., Hanaoka, F., Ahmad, S. I
  • Publisher: Adv. Exp. Med. Biol
• [Book] Methods Mol. Biol(Use of RNAi in C. elegans) (2008)
  • Author(s): Ohkumo, T., Masutani, C., Eki, T., Hanaoka, F
• [Remarks]
  • URL: http://www.fbs.osaka-u.ac.jp/jp/labo/091/
• [Remarks]
  • URL: http://www.fbs.osaka-u.ac.jp/jp/labo/091/
• [Remarks]
  • URL: http://www.fbs.osaka-u.ac.jp/jp/labo/091/