Y-family DNA polymerases in mammalian cells

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

DOI: 10.1007/s00018-009-0024-4

Cite this article as:
Guo, C., Kosarek-Stancel, J.N., Tang, TS. et al. Cell. Mol. Life Sci. (2009) 66: 2363. doi:10.1007/s00018-009-0024-4

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.

Keywords

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

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Caixia Guo
    • 1
    • 2
  • J. Nicole Kosarek-Stancel
    • 1
  • Tie-Shan Tang
    • 3
  • Errol C. Friedberg
    • 1
  1. 1.Laboratory of Molecular Pathology, Department of PathologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Beijing Institute of GenomicsChinese Academy of ScienceBeijingChina
  3. 3.State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of ZoologyChinese Academy of ScienceBeijingChina