| 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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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | X線結晶解析 / DNAポリメラーゼ / DNA複製 / DNA損傷 / 損傷乗り越えDNA合成 / X線結晶構造解析 / REV7 / REV3 / REV1 / タンパク質複合体 |
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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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