2016 Fiscal Year Final Research Report
Analyses of oxidative stress-dependent formation of MUTYH/MutSalpha complex
| Project/Area Number |
26340025
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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 |
Risk sciences of radiation and chemicals
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Research Collaborator |
HAYASHIDA Genki 九州大学, システム生命学府
SONG Yingxia 九州大学, 医学系学府
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | ミスマッチ修復 / 細胞死 / DNA損傷 / 8-オキソグアニン |
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| Outline of Final Research Achievements |
We observed an oxidative stress-dependent complex formation of MUTYH and mismatch repair factors. Using anti-FLAG antibody, we purified the complex from FLAG-tagged MUTYH expressing human cells. Western blot analyses revealed that the complex contained DNA polymerase δ and MLH 1 in addition to MSH 2, MSH 6, and PCNA. The interaction between MUTYH and MSH2 was also observed in the 8-oxo-dGua administered cells, suggesting that 8-oxoG is involved in the formation of this complex. In cells loaded with oxidative stress, transient mono-ubiquitination of PCNA occurs, but PCNA in this complex has not undergone ubiquitination. Certain MSH2 mutants found in Lynch syndrome and a DNA polymerase δ mutant do not form the oxidative stress-dependent complexes with MUTYH. These results suggested that DNA polymerase δ as well as MSH2 might be involved in molecular mechanisms underlying oxidative stress induced cell-death.
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| Free Research Field |
分子生物学
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