Y-family DNA polymerases in mammalian cells

Caixia Guo, J. Nicole Kosarek-Stancel, Tie Shan Tang, Errol C. Friedberg

Research output: Contribution to journalReview article

108 Scopus citations

Abstract

Eukaryotic genomes are replicated with high fidelity to assure the faithful transmission of genetic information from one generation to the next. The accuracy of replication relies heavily on the ability of replicative DNA polymerases to efficiently select correct nucleotides for the polymerization reaction and, using their intrinsic exonuclease activities, to excise mistakenly incorporated nucleotides. Cells also possess a variety of specialized DNA polymerases that, by a process called translesion DNA synthesis (TLS), help overcome replication blocks when unrepaired DNA lesions stall the replication machinery. This review considers the properties of the Y-family (a subset of specialized DNA polymerases) and their roles in modulating spontaneous and genotoxic-induced mutations in mammals. We also review recent insights into the molecular mechanisms that regulate PCNA monoubiquitination and DNA polymerase switching during TLS and discuss the potential of using Y-family DNA polymerases as novel targets for cancer prevention and therapy.

Original languageEnglish (US)
Pages (from-to)2363-2381
Number of pages19
JournalCellular and Molecular Life Sciences
Volume66
Issue number14
DOIs
StatePublished - Jul 1 2009

Keywords

  • Mutagenesis
  • PCNA
  • Polymerase switching
  • Replication foci
  • Somatic hypermutation
  • Translesion DNA synthesis
  • Y-family polymerase

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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