The Shu complex, which contains Rad51 paralogues, promotes DNA repair through inhibition of the Srs2 anti-recombinase

Mol Biol Cell. 2011 May;22(9):1599-607. doi: 10.1091/mbc.E10-08-0691. Epub 2011 Mar 3.

Abstract

The Shu complex, which contains RAD51 paralogues, is involved in the decision between homologous recombination and error-prone repair. We discovered a link to ribosomal DNA (rDNA) recombination when we found an interaction between one member of the Shu complex, SHU1, and UAF30, a component of the upstream activating factor complex (UAF), which regulates rDNA transcription. In the absence of Uaf30, rDNA copy number increases, and this increase depends on several functional subunits of the Shu complex. Furthermore, in the absence of Uaf30, we find that Shu1 and Srs2, an anti-recombinase DNA helicase with which the Shu complex physically interacts, act in the same pathway regulating rDNA recombination. In addition, Shu1 modulates Srs2 recruitment to both induced and spontaneous foci correlating with a decrease in Rad51 foci, demonstrating that the Shu complex is an important regulator of Srs2 activity. Last, we show that Shu1 regulation of Srs2 to double-strand breaks is not restricted to the rDNA, indicating a more general function for the Shu complex in the regulation of Srs2. We propose that the Shu complex shifts the balance of repair toward Rad51 filament stabilization by inhibiting the disassembly reaction of Srs2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Repair*
  • DNA, Fungal / genetics*
  • DNA, Ribosomal / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Plasmids / genetics
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism*
  • Recombination, Genetic
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / metabolism

Substances

  • DNA, Fungal
  • DNA, Ribosomal
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Shu1 protein, S cerevisiae
  • Transcription Factors
  • UAF30 protein, S cerevisiae
  • SRS2 protein, S cerevisiae
  • RAD51 protein, S cerevisiae
  • Rad51 Recombinase
  • DNA Helicases