| Project/Area Number |
22510063
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | Gakushuin University |
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Principal Investigator |
YOKOI Masayuki 学習院大学, 理学部生命科学科, 助教 (00322701)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | DNAポリメラーゼ / DNA損傷 / 損傷乗り越え複製 / 紫外線 / polη / 突然変異 / 損傷乗り起え複製 |
|---|
| Research Abstract |
DNA polymerase η (Polη), whose gene mutation is responsible for the inherited disorder xeroderma pigmentosum variant (XP-V), carries out accurate and efficient TLS against cyclobutane pyrimidine dimer (CPD). Since Polη interacts with Polι and REV1, it is suggested that Polη plays a role in recruitment of these TLS polymerases at lesion site. But it is unclear whether UV sensitivity of XP-V patients is caused not only by defect of Polη activity but also by dysfunction of network between Polη and other TLS polymerases. Here, we examined whether the TLS polymerase network via Polη is important for replicative bypass of CPDs and DNA damage tolerance induced by UV in mouse cells. We observed that UV sensitivity of Polη-deficient mouse cells was moderately rescued by the expression of inactive Polη. Moreover, this recovery of cellular UV sensitivity was mediated by the interaction between Polη and REV1. However, expression of inactive mutant Polη was not able to suppress the striking incidence of UV-induced mutation observed in Polη-deficient cells. Finally we demonstrated that REV1 and Polκ are involved in mutagenic DNA damage tolerance via Polη-REV1 interaction when Polη was failed to bypass its cognate substrates.
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