2009 Fiscal Year Final Research Report
Structural biology of human REV1, REV3 and REV7 complex
| Project/Area Number |
20770089
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Structural biochemistry
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| Research Institution | Yokohama City University |
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Principal Investigator |
HASHIMOTO Hiroshi Yokohama City University, 生命ナノシステム科学研究科, 助教 (40336590)
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| Project Period (FY) |
2008 – 2009
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| Keywords | X線結晶解析 |
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| Research Abstract |
DNA polymerase ζ (Polζ) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS). Polζ consists of two subunits: the catalytic REV3, which belongs to B-family DNA polymerase, and the non-catalytic REV7. REV7 also interacts with REV1 polymerase, which is an error-prone Y-family DNA polymerase and also involved in TLS. Cells deficient in one of the three REV proteins and those deficient in all three proteins show similar phenotype, indicating the functional collaboration of the three REV proteins. REV7 interacts with both REV3 and REV1 polymerases, but the structure of REV7 or REV3, as well as the structural and functional basis of the REV1-REV7 and REV3-REV7 interactions remains unknown. Here we show the first crystal structure of human REV7 in complex with a fragment of human REV3 polymerase (residues 1847-1898) and reveal the mechanism underlying REV7-REV3 interaction. The structure indicates that the interaction between REV7 and REV3 creates a structural interface for REV1-binding. Furthermore, we show that the REV7-mediated interactions are responsible for DNA-damage tolerance. Our results highlight the function of REV7 as an adapter protein to recruit Polζ to a lesion site. REV7 is alternatively called MAD2B or MAD2L2 and also involved in various cellular functions such as signal transduction and cell-cycle regulation. Our results will provide a general structural basis for understanding the REV7-interaction.
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[Presentation] ヒトREV7の構造生物学的研究2010
Author(s)
原幸大, 橋本博, 村雲芳樹, 小林俊介, 小亀敏明, 雲財悟, 明石知子, 武田俊一, 清水敏之, 佐藤衛
Organizer
PFシンポジウム
Place of Presentation
つくば
Year and Date
20100308-20100309
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[Presentation] Crystal structure of REV72009
Author(s)
Kodai Hara, Toshiyuki Shimizu, Yoshiki Murakumo, Tomo Hanafusa, Haruo Ohmori, Mamoru Sato, Hiroshi Hashimoto
Organizer
ACA Meeting
Place of Presentation
Toronto
Year and Date
20090725-20090730
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