2017 Fiscal Year Final Research Report
CPT (DNA topoisomerase I inhibitor) and DNA replication fork
| Project/Area Number |
15K07009
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
SEKI Masayuki 東北医科薬科大学, 薬学部, 教授 (70202140)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | DNA複製 / フォーク / Tipin / WRNIP1 / Rad52 / DNAトポイソメラーゼI / カンプトテシン / MCMヘリカーゼ |
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| Outline of Final Research Achievements |
Main findings are as follows; (1) Excess DNA replication initiation factor Cdt1 inhibits MCM helicase activity in frog eggs extract. (2) Chicken DT40 TIPIN KO cells shows CTP (DNA topoisomerase I inhibitor) hypersensitivity. Under low dose CPT exposure, DNA double strand breaks are accumulated in TIPIN KO, leading to hyper checkpoint activation. (3) After UV irradiation, UV sensitivity and UV-induced hyper mutation of DT40 Polh single KO cells are almost completely suppressed by WRNIP1 gene knockout, suggesting that WRNIP1 acts upstream of Polh. (4) One of translation polymerases, PriPol is down-regulated by overproduction of WRNIP1. PriPol is the best candidate for error-free translesion polymerase on UV-damaged DNA in the absence of both WRNIP1 and Polh.
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| Free Research Field |
分子細胞生物学
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