ユビキチン化によるDNA複製停止解除の制御機構の解明

• 研究課題/領域番号: 19810007
• 研究種目: 若手研究(スタートアップ)
• 配分区分: 補助金
• 研究分野: 放射線・化学物質影響科学
• 研究機関: 京都大学
• 研究代表者: 茂木 章 京都大学, 大学院・医学研究科, 助教 (80452332)
• 研究期間 (年度): 2007 – 2008
• 研究課題ステータス: 完了 (2008年度)
• 配分額: 3,075千円 (直接経費: 2,670千円、間接経費: 405千円); 2008年度: 1,755千円 (直接経費: 1,350千円、間接経費: 405千円); 2007年度: 1,320千円 (直接経費: 1,320千円)
• キーワード: 組換え修復 / 複製後修復 / ユビキチン化 / 組み替え修復 / 組替え修復

研究概要

本研究では、ヒトユビキチンリガーゼHLTFが、出芽酵母Rad5の機能的ホモログであり、PCNAのポリユビキチン化を介して、複製ポリメラーゼの停止解除を促進することを明らかにした(PNAS 2008論文発表)。また、 DNA二本鎖切断の修復の際にUBC13と共役して働くユビキチンリガーゼの一つRNF8の遺伝子破壊DT40株を作製し、その表現型解析を行った。これにより、RNF8が相同組み替え修復を促進することを明らかにした(Keystone Symposia 2009学会発表)。

研究成果

• [雑誌論文] 抗がん剤で考えるDNA組み換えの制御機構 (2009)
  • 著者名/発表者名: 茂木章, 武田俊一
  • 雑誌名: タンパク質・核酸・酵素別冊 54(4) ページ: 450-458
• [雑誌論文] 抗がん剤で考えるDNA組み換えの制御機構 (2009)
  • 著者名/発表者名: 茂木章, 武田俊一
  • 雑誌名: タンパク質・核酸・酵素別冊 54 ページ: 450-458
• [雑誌論文] Roles of proteasome in DNA repair : impacts of proteasome inhibiotors on cancer therapy (2009)
  • 著者名/発表者名: Akira Motegi, Yasuhiro Murakawa, Shunichi Takeda
  • 雑誌名: Cancer Letters
  • 査読あり
• [雑誌論文] Roles of proteasome in DNA repair : impacts of proteasome inhibiotors on cancer therapy (2008)
  • 著者名/発表者名: Akira Motegi, Yasuhiro Murakawa, and Shunichi Takeda
  • 雑誌名: Cancer lett (in press)
  • 査読あり
• [雑誌論文] Lysine 63-linked polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks (2008)
  • 著者名/発表者名: Akira Motegi, Hung-jiun Liaw, Kyoo-Young Lee, Henk P. Roest, Alex Maas, Xiaoli Wu, Helen Moinova, Sanford D. Markowitz, Hao Ding, Jan H. J. Hoeijmakers, and Kyungjae Myung
  • 雑誌名: Proc. Natl. Acad. Sci. USA 105 ページ: 12411-12416
  • 査読あり
• [雑誌論文] Mph1 promotes gross chromosomal rearrangement through partial inhibition of homologous recombination J (2008)
  • 著者名/発表者名: Soma Banerjee, Stephanie Smith, Ji-Hyun Oum, Hung-Jiun Liaw, Ji-Young Hwang, Nilabja Sikdar, Akira Motegi, Sang Eun Lee, and Kyungjae Myung
  • 雑誌名: Cell Biol 181 ページ: 1083-1093
  • 査読あり
• [雑誌論文] ユビキチン化によるDNA修復の制御機構 (2008)
  • 著者名/発表者名: 茂木章, 村川泰裕, 武田俊一
  • 雑誌名: 実験医学別冊 26(2) ページ: 62-70
  • NAID: 40015691605
• [雑誌論文] Lysine 63-linked polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks (2008)
  • 著者名/発表者名: Akira Motegi, Hung-jiun Liaw. Kyoo-Young Lee, Henk P. Roest, Alex Maas, Xiaoli Wu. Helen Moinova, Sanford D. Markowitz, Hao Ding, Jan H. J. Hoeijmakers, Kyungjae Myung
  • 雑誌名: Proc. Natl. Acad. Sci. USA 105 ページ: 12411-12416
  • 査読あり
• [雑誌論文] Mphl promotes gross chromosomal rearrangement through partial inhibition of homologous recombination (2008)
  • 著者名/発表者名: Soma Banerjee, Stephanie Smith, Ji-Hyun Oum, Hung-Jiun Liaw, Ji-Young Hwang, Nilabja Sikdar, Akira Motegi, Sang Eun Lee, Kyungjae Myung
  • 雑誌名: J. Cell Biol. 181 ページ: 1083-1093
  • 査読あり
• [雑誌論文] ユビキチン化によるDNA修復の制御機構 (2008)
  • 著者名/発表者名: 茂木 章、村川泰裕、武田俊一
  • 雑誌名: 羊土社 26(2) ページ: 62-70
  • NAID: 40015691605
• [雑誌論文] ユビキチン化によるDNA修復の制御機構 (2007)
  • 著者名/発表者名: 茂木章, 村川泰裕, 武田俊一
  • 雑誌名: 細胞工学 26(11) ページ: 1290-1295
  • NAID: 40015691605
• [雑誌論文] ユビキチン化によるDNA修復の制御機構 (2007)
  • 著者名/発表者名: 茂木 章、村川泰裕、武田俊一
  • 雑誌名: 細胞工学 26(11) ページ: 1290-1295
  • NAID: 40015691605
• [学会発表] Functional analysis of the ubiquitin ligase RNF8 in DNA repair (2009)
  • 著者名/発表者名: Saho Era, Yohei Kasaishi, Shunichi Takeda, Akira Motegi
  • 学会等名: Keystone Symposia (Genome Instability and Repair)
  • 発表場所: Taos, NM, USA
  • 年月日: 2009-03-02
• [学会発表] Functional analysis of the ubiquitin ligase RNF8 in DNA repair Keystone Symposia (2009)
  • 著者名/発表者名: Saho Era, Yohei Kasaishi, Shunichi Takeda, and Akira Motegi
  • 学会等名: Genome Instability and Repair
  • 発表場所: Taos, NM, USA
• [学会発表] Lysine 63-linked polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks, Gordon Research Conference (2009)
  • 著者名/発表者名: Akira Motegi, Hung-jiun Liaw, Kyoo-Young Lee, Henk P. Roest, Alex Maas, Xiaoli Wu, Helen Moinova, Sanford D. Markowitz, Hao Ding, Jan H. J. Hoeijmakers, and Kyungjae Myung
  • 学会等名: Mammalian DNA Repair
  • 発表場所: Ventura, CA, USA
• [学会発表] Human ubiquitin ligases HLTF and SHPRH prevents genomic instability from stalled replication forks, Gordon Research Conference (2009)
  • 著者名/発表者名: Hung-jiun Liaw, Akira Motegi, Kyoo-Young Lee, Henk P. Roest, Alex Maas, Xiaoli Wu, Helen Moinova, Sanford D. Markowitz, Hao Ding, Jan H. J. Hoeijmakers, and Kyungjae Myung
  • 学会等名: Mammalian DNA Repair
  • 発表場所: Ventura, CA, USA
• [学会発表] Chicken Rap80 promotes repair of toposiomerase II poison-induced DNA damage, Gordon Research Conference (2009)
  • 著者名/発表者名: Junko Iijima, Akira Motegi, Toru Fukushima, Yoshihito Taniguchi, and Shunichi Takeda
  • 学会等名: Mammalian DNA Repair
  • 発表場所: Ventura, CA, USA
• [学会発表] Lysine 63-linked polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks (2009)
  • 著者名/発表者名: Akira Motegi, Hung-jiun Liaw, Kyoo-Young Lee, Henk P. Roest, Alex Maas, Xiaoli Wu, Helen Moinova, Sanford D. Markowitz, Hao Dins, Jan H. J. Hoeijoakers, Kyungjae Myung
  • 学会等名: Gordon Research Conference (Mammalian DNA Repair)
  • 発表場所: Ventura, CA, USA
• [学会発表] Human ubiquitin ligases HLTF and SHPRH prevents genomic instability from stalled replication forks (2009)
  • 著者名/発表者名: Hung-jiun Liaw, Akira Motegi, Kyoo-Young Lee, Henk P. Roest, Alex Maas, Xiaoli Wu, Helen Moinova. Sanford D. Markowitz, Hao Ding, Jan H. J. Hoeijmakers, Kyungjae Myung
  • 学会等名: Gordon Research Conference (Mammalian DNA Repair)
  • 発表場所: Ventura, CA, USA
• [学会発表] Chicken Rap80 promotes repair of toposiomerase II poison-induced DNA damage (2009)
  • 著者名/発表者名: Junko Iijima, Akira Motegi, Toru Fukushima, Yoshihito Taniguchi, Shunichi Takeda
  • 学会等名: Gordon Research Conference (Mammalian DNA Repair)
  • 発表場所: Ventura, CA, USA
• [学会発表] Lysine 63-linked polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks (2009)
  • 著者名/発表者名: Akira Motegi, Hung-jiun Liaw, Kyoo-Young Lee, Henk P. Roest, Alex Maas, Xiaoli Wu. Helen Moinova, Sanford D. Markowitz, Hao Ding, Jan H. J. Hoeijmakprs, Shunichi Takeda, Kyungjae Myung
  • 学会等名: The 6th International 3R Symposium 2008
  • 発表場所: Tsumagoi, Japan
• [学会発表] PTIP Is Implicated in a Late Step of Homologous Recombination-mediated Double Strand Breaks (DSBs) Repair (2008)
  • 著者名/発表者名: Xin Wang, Katsuya Takenaka, Akira Motegi, Shunichi Takeda
  • 学会等名: The International Ataxia-Telangiectasia Workshop
  • 発表場所: Otsu, Japan
  • 年月日: 2008-04-24
• [学会発表] Human SHPRH and HLTF suppress genomic instability through the lysine-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) (2008)
  • 著者名/発表者名: Akira Motegi, Hung-jiun Liaw, Raman Sood, Helen Moinova, Sanford D. Markowitz, Pu Paul Liu, Kyungjae Myung, Shumichi Takeda
  • 学会等名: The International Ataxia-Telangiectasia Workshop
  • 発表場所: Otsu, Japan
  • 年月日: 2008-04-23
• [学会発表] Lysine 63-linked polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks (2008)
  • 著者名/発表者名: Akira Motegi, Hung-jiun Liaw, Kyoo-Young Lee, Henk P. Roest, Alex Maas, Xiaoli Wu, Helen Moinova, Sanford D. Markowitz, Hao Ding, Jan H. J. Hoeijmakers, Shunichi Takeda, and Kyungjae Myung
  • 学会等名: The 6th International 3R Symposium 2008
  • 発表場所: Tsumagoi, Japan
• [学会発表] Human SHPRH and HLTF suppress genomic instability through the lysine-63-linked polyubiquitination of proliferating cell nuclear antigen(PCNA) (2008)
  • 著者名/発表者名: Akira Motegi, Hung-jiun Liaw, Raman Sood, Helen Moinova, Sanford D. Markowitz, Pu Paul Liu, Kyungjae Myung, and Shunichi Takeda
  • 学会等名: The International Ataxia-Telangiectasia Workshop2008
  • 発表場所: Otsu, Japan
• [学会発表] Human PTIP Is Implicated in a Late Step of Homologous Recombination-mediated Double Strand Breaks(DSBs)Repair (2008)
  • 著者名/発表者名: Xin Wang, Akira Motegi, and Shunichi Takeda
  • 学会等名: The International Ataxia-Telangiectasia Workshop 2008
  • 発表場所: Otsu, Japan
• [学会発表] Human post-replication repair pathway by the Rad5 homolog SHPRH in the suppression of genomic instability (2008)
  • 著者名/発表者名: Hungjiun Liaw, Akira Motegi, Kyoo-Young Lee, and Kyungjae Myung
  • 学会等名: Keystone Symposia (Genome Instability and Repair)
  • 発表場所: Santa Fe, NM, USA
• [学会発表] Human SHPRH and HLTF suppress genomic instability through the lysine-63-linked polyubiquitination of PCNA (2007)
  • 著者名/発表者名: Akira Motegi
  • 学会等名: The 30th Annual Meeting of MBSJ (BMB 2007)
  • 発表場所: 横浜
  • 年月日: 2007-12-15
• [学会発表] Human SHPRH and HLTF suppress genome instability through PCNA polyubiquitination (2007)
  • 著者名/発表者名: Akira Motegi, Hungjiun Liaw, Kyoo-Young Lee, Shunichi Takeda, and Kyungjae Myung
  • 学会等名: 2007 Annual Meeting of Molecular Biology Society of Japan(Symposium)
  • 発表場所: Yokohama, Japan