| Project/Area Number |
16H04755
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | University of Shizuoka |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
原 幸大 静岡県立大学, 薬学部, 講師 (80729343)
菱木 麻美 静岡県立大学, 薬学部, 助教 (60571172)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | DNA損傷応答 / X線結晶構造解析 / DNA修復 / 構造生物学 / タンパク質 |
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| Outline of Final Research Achievements |
Template switching (TS), also known as the damage avoidance path-way, in which one newly synthesized strand is utilized as an undamaged template for replication by replicative polymerases, is an error-free process. Several DNA helicases including HLTF and ZRANB3 are crucially engaged in this pathway and these are involved in reversal of the replication fork. HLTF and ZRANB3, might be involved in the early and late stages of the TS, respectively. Also, PARI that is recently identified protein that inhibit homologous recombination thereby stimulating TS. In this study, crystal structures of the HLTF N-terminal domain bound to DNA and PCNA bound to the ZRANB3 peptides have been determined. These structures reveal interactions of these protein complexes and mechanisms of these interactions.
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| Academic Significance and Societal Importance of the Research Achievements |
私たちのDNAは毎日様々な要因によって損傷を受けているが、適切な修復機構によって直されている。しかしDNAのコピーが作られるときに損傷が生じるとDNAのコピーが途中で止まってしまい、細胞にとって好ましくない。このような状況を回避する手段の一つがテンプレートスイッチ（TS）である。TSは損傷の無いDNAを使ってコピーを作る。その一方で、TSはがん細胞が抗がん剤抵抗性を獲得する要因の一つである。しがたって、TSのメカニズムを解明することで新たな創薬の手がかりを得ることができる。本研究ではTSを行うためのタンパク質とDNAとの相互作用、タンパク質とタンパク質との相互作用メカニズムをの一端を解明した。
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