A novel function of DNA polymerase ζ regulated by PCNA

Matthew R. Northam, Parie Garg, Dmitri M. Baitin, Peter M.J. Burgers, Polina V. Shcherbakova

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

DNA polymerase ζ (Polζ) participates in translesion DNA synthesis and is involved in the generation of the majority of mutations induced by DNA damage. The mechanisms that license access of Polζ to the primer terminus and regulate the extent of its participation in genome replication are poorly understood. The Polζ-dependent damage-induced mutagenesis requires monoubiquitination of proliferating cell nuclear antigen (PCNA) that is triggered by exposure to mutagens. We show that Polζ contributes to DNA replication and causes mutagenesis not only in response to DNA damage but also in response to malfunction of normal replicative machinery due to mutations in replication genes. These replication defects lead to ubiquitination of PCNA even in the absence of DNA damage. Unlike damage-induced mutagenesis, the Polζ-dependent spontaneous mutagenesis in replication mutants is reduced in strains defective in both ubiquitination and sumoylation of Lys164 of PCNA. Additionally, studies of a PCNA mutant defective for functional interactions with Polζ, but not for monoubiquitination by the Rad6/Rad18 complex demonstrate a role for PCNA in regulating the mutagenic activity of Polζ separate from its modification at Lys164.

Original languageEnglish (US)
Pages (from-to)4316-4325
Number of pages10
JournalEMBO Journal
Volume25
Issue number18
DOIs
StatePublished - Sep 20 2006

Keywords

  • DNA polymerase ζ
  • DNA replication
  • Mutagenesis
  • PCNA
  • Ubiquitination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Northam, M. R., Garg, P., Baitin, D. M., Burgers, P. M. J., & Shcherbakova, P. V. (2006). A novel function of DNA polymerase ζ regulated by PCNA. EMBO Journal, 25(18), 4316-4325. https://doi.org/10.1038/sj.emboj.7601320