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- W2064853771 abstract "Human DNA polymerase kappa (hpol κ) is the only Y-family member to preferentially insert dAMP opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) during translesion DNA synthesis. We have studied the mechanism of action by which hpol κ activity is modulated by the Werner syndrome protein (WRN), a RecQ helicase known to influence repair of 8-oxo-dG. Here we show that WRN stimulates the 8-oxo-dG bypass activity of hpol κ in vitro by enhancing the correct base insertion opposite the lesion, as well as extension from dC:8-oxo-dG base pairs. Steady-state kinetic analysis reveals that WRN improves hpol κ-catalyzed dCMP insertion opposite 8-oxo-dG ∼10-fold and extension from dC:8-oxo-dG by 2.4-fold. Stimulation is primarily due to an increase in the rate constant for polymerization (kpol), as assessed by pre-steady-state kinetics, and it requires the RecQ C-terminal (RQC) domain. In support of the functional data, recombinant WRN and hpol κ were found to physically interact through the exo and RQC domains of WRN, and co-localization of WRN and hpol κ was observed in human cells treated with hydrogen peroxide. Thus, WRN limits the error-prone bypass of 8-oxo-dG by hpol κ, which could influence the sensitivity to oxidative damage that has previously been observed for Werner's syndrome cells." @default.
- W2064853771 created "2016-06-24" @default.
- W2064853771 creator A5009406752 @default.
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- W2064853771 creator A5015360214 @default.
- W2064853771 creator A5031445368 @default.
- W2064853771 creator A5052078607 @default.
- W2064853771 date "2014-10-07" @default.
- W2064853771 modified "2023-10-10" @default.
- W2064853771 title "The Werner syndrome protein limits the error-prone 8-oxo-dG lesion bypass activity of human DNA polymerase kappa" @default.
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- W2064853771 doi "https://doi.org/10.1093/nar/gku913" @default.
- W2064853771 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4231769" @default.
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- W2064853771 hasPublicationYear "2014" @default.
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