The role of hRev7, the accessory subunit of hPolζ, in translesion synthesis past DNA damage induced by benzo[a]pyrene diol epoxide (BPDE) |
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Authors: | Jessica A Neal Kathryn L Fletcher J Justin McCormick Veronica M Maher |
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Institution: | (1) Carcinogenesis Laboratory, Department of Microbiology & Molecular Genetics, and Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824-1302, USA |
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Abstract: | Background DNA polymerase zeta (Polζ) is a specialized DNA polymerase that, unlike classical replicative polymerases, is capable of replicating
past DNA lesions, i.e. of performing translesion synthesis (TLS). The catalytic subunit of hPolζ, hRev3, has been shown to
play a critical role in DNA damage-induced mutagenesis in human cells, but less is known about the role of hRev7, the accessory
subunit of hPolζ, in such mutagenesis. To address this question, we recently generated human fibroblasts with very significantly
reduced levels of hRev7 protein and demonstrated that hRev7 is required to protect cells from ultraviolet(254 nm) (UV) radiation-induced cytotoxicity and mutagenesis (McNally et al., DNA Repair 7 (2008) 597-604). The goal of the present
study was to determine whether hRev7 is similarly involved in the tolerance of DNA damage induced by benzoa]pyrene diol epoxide
(BPDE), the reactive form of the widespread environmental carcinogen benzoa]pyrene. |
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