Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ

Jung Hoon Yoon, Jeseong Park, Juan Conde, Maki Wakamiya, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Translesion synthesis (TLS) DNA polymerases (Pols) promote replication through DNA lesions; however, little is known about the protein factors that affect their function in human cells. In yeast, Rev1 plays a noncatalytic role as an indispensable component of Polζ, and Polζ together with Rev1 mediates a highly mutagenic mode of TLS. However, how Rev1 functions in TLS and mutagenesis in human cells has remained unclear. Here we determined the role of Rev1 in TLS opposite UV lesions in human and mouse fibroblasts and showed that Rev1 is indispensable for TLS mediated by Polη, Polι, and Polκ but is not required for TLS by Polζ. In contrast to its role in mutagenic TLS in yeast, Rev1 promotes predominantly error-free TLS oppositeUV lesions in humans. The identification of Rev1 as an indispensable scaffolding component for Polη, Polι, and Polκ, which function in TLS in highly specialized ways opposite a diverse array of DNA lesions and act in a predominantly error-free manner, implicates a crucial role for Rev1 in the maintenance of genome stability in humans.

Original languageEnglish (US)
Pages (from-to)2588-2602
Number of pages15
JournalGenes and Development
Volume29
Issue number24
DOIs
StatePublished - Dec 15 2015

Keywords

  • CII mutation analyses
  • DNA lesion bypass
  • DNA repair
  • UV damage

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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