Ubiquitin-dependent regulation of DNA replication arrest

• Project/Area Number: 19810007
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyoto University
• Principal Investigator: MOTEGI Akira Kyoto University, 大学院・医学研究科, 助教 (80452332)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,075,000 (Direct Cost: ¥2,670,000、Indirect Cost: ¥405,000); Fiscal Year 2008: ¥1,755,000 (Direct Cost: ¥1,350,000、Indirect Cost: ¥405,000); Fiscal Year 2007: ¥1,320,000 (Direct Cost: ¥1,320,000)
• Keywords: 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

Research Abstract

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)。

Research Products

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