2012 Fiscal Year Final Research Report
Physiological role of protein-protein interaction among translesion DNA polymerases in cellular resistance to ultraviolet light
| 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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| Keywords | DNAポリメラーゼ / DNA損傷 / 損傷乗り越え複製 / 紫外線 |
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| 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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[Journal Article] Stalled Polη at its cognate substrate initiates an alternative translesion synthesis pathway via interaction with REV12012
Author(s)
Ito, W*., Yokoi, M*., Sakayoshi, N., Sakurai, Y., Akagi, J., Mitani, H., and Hanaoka, F. (*: equal contribution)
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Journal Title
Genes to Cells
Volume: 17
Pages: 98-108
Peer Reviewed
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[Presentation] Rev1-dependent activity of Polκcontributes to translesion synthesis past UV-induced DNA lesions2012
Author(s)
Suzuki, K., Akagi, J., Ohashi, E., Yokoi, M., Ohmori,H., and Hanaoka, F
Organizer
第35回日本分子生物学会年会
Place of Presentation
福岡
Year and Date
2012-12-12
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[Presentation] Establishment of mouse expressing inactive DNA polymerase η2012
Author(s)
Morita, D., Sakurai, Y., Sakayoshi, N., Ito, W., Yokoi, M., Hanaoka, F
Organizer
第35回日本分子生物学会年会
Place of Presentation
福岡
Year and Date
2012-12-12
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[Presentation] Polκ contributes to suppression of UV-induced mutagenesis2011
Author(s)
Suzuki, K., Akagi, J., Ohashi, E., Yokoi, M., Ohmori.H., and Hanaoka, F
Organizer
第34回日本分子生物学会年会
Place of Presentation
横浜
Year and Date
2011-12-14
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[Presentation] Roles of DNA polymeraseη and ι in UV-induced mutagenesis and DNA damage tolerance2010
Author(s)
Sakurai, Y., Yokoi, M., Ohkumo, T., Tsukamoto, T., Tatematsu, M., Wei, M., Wanibuchi, H., Hanaoka, F
Organizer
BMB2010
Place of Presentation
神戸
Year and Date
2010-12-08
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[Presentation] UV照射DNAの損傷乗り越え複製におけるDNAポリメラーゼイータとイオタの生体内での役割2010
Author(s)
Sakurai, Y., Yokoi, M., Tsukamoto, T., Tatematsu, M., Wei, M., Wanibuchi, H., Hanaoka, F
Organizer
第69回日本癌学会学術総会
Place of Presentation
大阪
Year and Date
2010-09-24
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[Presentation] Roles of DNA polymerase η and ι in translesion synthesis past UVB-induced DNA lesions in vivoGordon Research Conference2010
Author(s)
Yokoi, M., Sakurai, Y., Tsukamoto, T., Tatematsu, M., Hanaoka, F
Organizer
Mutagenesis
Place of Presentation
Waterville, USA
Year and Date
2010-08-04
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