A non-catalytic function of Rev1 in translesion DNA synthesis and mutagenesis is mediated by its stable interaction with Rad5

Lisha Kuang, Haiping Kou, Zhongwen Xie, Ying Zhou, Xingang Feng, Lei Wang, Zhigang Wang

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

DNA damage tolerance consisting of template switching and translesion synthesis is a major cellular mechanism in response to unrepaired DNA lesions during replication. The Rev1 pathway constitutes the major mechanism of translesion synthesis and base damage-induced mutagenesis in model cell systems. Rev1 is a dCMP transferase, but additionally plays non-catalytic functions in translesion synthesis. Using the yeast model system, we attempted to gain further insights into the non-catalytic functions of Rev1. Rev1 stably interacts with Rad5 (a central component of the template switching pathway) via the C-terminal region of Rev1 and the N-terminal region of Rad5. Supporting functional significance of this interaction, both the Rev1 pathway and Rad5 are required for translesion synthesis and mutagenesis of 1,N6-ethenoadenine. Furthermore, disrupting the Rev1-Rad5 interaction by mutating Rev1 did not affect its dCMP transferase, but led to inactivation of the Rev1 non-catalytic function in translesion synthesis of UV-induced DNA damage. Deletion analysis revealed that the C-terminal 21-amino acid sequence of Rev1 is uniquely required for its interaction with Rad5 and is essential for its non-catalytic function. Deletion analysis additionally implicated a C-terminal region of Rev1 in its negative regulation. These results show that a non-catalytic function of Rev1 in translesion synthesis and mutagenesis is mediated by its interaction with Rad5.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalDNA Repair
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2013

Bibliographical note

Funding Information:
We thank Jon Klein of the University of Louisville for performing mass spectrometry analysis. We thank Christopher Lawrence of the University of Rochester for providing us the yeast strain CL1265-7C. This work was supported by a Kentucky Lung Cancer Research grant.

Keywords

  • DNA damage
  • Damage tolerance
  • Rev1
  • Translesion synthesis
  • Y family DNA polymerase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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