Srs2 overexpression reveals a helicase-independent role at replication forks that requires diverse cell functions

DNA Repair (Amst). 2011 May 5;10(5):506-17. doi: 10.1016/j.dnarep.2011.02.004. Epub 2011 Apr 1.


Srs2 is a 3'-5' DNA helicase that regulates many aspects of DNA metabolism in Saccharomyces cerevisiae. It is best known for its ability to counteract homologous recombination by dismantling Rad51 filaments, but is also involved in checkpoint activation, adaptation and recovery, and in resolution of late recombination intermediates. To further address its biological roles and uncover new genetic interactions, we examined the consequences of overexpressing SRS2 as well as two helicase-dead mutants, srs2-K41A and srs2-K41R, in the collection of 4827 yeast haploid deletion mutants. We identified 274 genes affecting a large variety of cellular functions that are required for cell growth when SRS2 or its mutants are overexpressed. Further analysis of these interactions reveals that Srs2 acts independently of its helicase function at replication forks likely through its recruitment by the sumoylated PCNA replication clamp. This helicase-independent function is responsible for the negative interactions with DNA metabolism genes and for the toxicity of SRS2 overexpression in many of the diverse cellular pathways revealed in our screens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism*
  • DNA Replication / genetics*
  • Gene Expression / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal / genetics
  • Microbial Viability / genetics
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Binding
  • Rad51 Recombinase / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sumoylation / physiology


  • Mutant Proteins
  • Proliferating Cell Nuclear Antigen
  • Saccharomyces cerevisiae Proteins
  • SRS2 protein, S cerevisiae
  • Rad51 Recombinase
  • DNA Helicases