The polymerase eta translesion synthesis DNA polymerase acts independently of the mismatch repair system to limit mutagenesis caused by 7,8-dihydro-8-oxoguanine in yeast.

Published

Journal Article

Reactive oxygen species are ubiquitous mutagens that have been linked to both disease and aging. The most studied oxidative lesion is 7,8-dihydro-8-oxoguanine (GO), which is often miscoded during DNA replication, resulting specifically in GC --> TA transversions. In yeast, the mismatch repair (MMR) system repairs GO.A mismatches generated during DNA replication, and the polymerase eta (Poleta) translesion synthesis DNA polymerase additionally promotes error-free bypass of GO lesions. It has been suggested that Poleta limits GO-associated mutagenesis exclusively through its participation in the filling of MMR-generated gaps that contain GO lesions. In the experiments reported here, the SUP4-o forward-mutation assay was used to monitor GC --> TA mutation rates in strains defective in MMR (Msh2 or Msh6) and/or in Poleta activity. The results clearly demonstrate that Poleta can function independently of the MMR system to prevent GO-associated mutations, presumably through preferential insertion of cytosine opposite replication-blocking GO lesions. Furthermore, the Poleta-dependent bypass of GO lesions is more efficient on the lagging strand of replication and requires an interaction with proliferating cell nuclear antigen. These studies establish a new paradigm for the prevention of GO-associated mutagenesis in eukaryotes.

Full Text

Duke Authors

Cited Authors

  • Mudrak, SV; Welz-Voegele, C; Jinks-Robertson, S

Published Date

  • October 2009

Published In

Volume / Issue

  • 29 / 19

Start / End Page

  • 5316 - 5326

PubMed ID

  • 19635811

Pubmed Central ID

  • 19635811

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

Digital Object Identifier (DOI)

  • 10.1128/MCB.00422-09

Language

  • eng

Conference Location

  • United States