BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules

Cell. 2007 Jul 27;130(2):259-72. doi: 10.1016/j.cell.2007.05.035.

Abstract

Bloom's helicase (BLM) is thought to prevent crossing-over during DNA double-strand-break repair (DSBR) by disassembling double-Holliday junctions (dHJs) or by preventing their formation. We show that the Saccharomyces cerevisiae BLM ortholog, Sgs1, prevents aberrant crossing-over during meiosis by suppressing formation of joint molecules (JMs) comprising three and four interconnected duplexes. Sgs1 and procrossover factors, Msh5 and Mlh3, are antagonistic since Sgs1 prevents dHJ formation in msh5 cells and sgs1 mutation alleviates crossover defects of both msh5 and mlh3 mutants. We propose that differential activity of Sgs1 and procrossover factors at the two DSB ends effects productive formation of dHJs and crossovers and prevents multichromatid JMs and counterproductive crossing-over. Strand invasion of different templates by both DSB ends may be a common feature of DSBR that increases repair efficiency but also the likelihood of associated crossing-over. Thus, by disrupting aberrant JMs, BLM-related helicases maximize repair efficiency while minimizing the risk of deleterious crossing-over.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Chromatids / metabolism*
  • Chromatids / ultrastructure
  • Crossing Over, Genetic / genetics*
  • DNA Breaks, Double-Stranded
  • DNA Helicases / chemistry*
  • DNA, Cruciform / metabolism
  • DNA-Binding Proteins / metabolism
  • Meiosis
  • Models, Genetic
  • Molecular Weight
  • Mutation / genetics
  • RecQ Helicases / metabolism*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Homology, Amino Acid*
  • Sister Chromatid Exchange
  • Transcription Factors / metabolism

Substances

  • DNA, Cruciform
  • DNA-Binding Proteins
  • NDT80 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Adenosine Triphosphatases
  • Bloom syndrome protein
  • SGS1 protein, S cerevisiae
  • DNA Helicases
  • RecQ Helicases