Mph1 and Mus81-Mms4 prevent aberrant processing of mitotic recombination intermediates

Gerard Mazón1, Lorraine S Symington

  • 1Department of Microbiology & Immunology, Columbia University Medical Center, New York, NY 10032, USA.

Molecular Cell
|October 15, 2013
PubMed

Insights

The Saccharomyces cerevisiae Mph1 helicase prevents genome rearrangements by removing DNA repair intermediates. Loss of Mph1 or nucleases impairs double-strand break repair, leading to problematic joint molecule accumulation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Homology-dependent repair of double-strand breaks (DSBs) can lead to loss of heterozygosity and genome rearrangements.
  • Ectopic recombination poses a risk for genomic instability.

Purpose of the Study:

  • To investigate the role of Saccharomyces cerevisiae Mph1 helicase in preventing crossovers between ectopic sequences.
  • To elucidate the roles of nucleases Mus81-Mms4, Rad1-Rad10, and Yen1 in DSB repair pathways.

Main Methods:

  • Genetic analysis of Saccharomyces cerevisiae mutants lacking key DNA repair proteins (Mph1, Mus81-Mms4, Rad1-Rad10, Yen1).
  • Observation of DNA repair intermediates, including joint molecules (JMs) and Holliday junctions (HJs).

Main Results:

  • Mph1 prevents crossovers by removing substrates for Mus81-Mms4 and Rad1-Rad10 cleavage.
  • Cells lacking Mph1 and the three nucleases exhibit severe defects in DSB repair.
  • Ectopic JMs accumulate in mph1Δ and mus81Δ mutants, with mus81Δ JMs containing single HJs, hindering processing by the Sgs1-Top3-Rmi1 complex (STR).

Conclusions:

  • Mph1 and Mus81-Mms4 likely recognize early strand exchange intermediates in DSB repair.
  • These proteins direct repair towards noncrossover or crossover outcomes, respectively.
  • The study highlights the coordinated action of helicases and nucleases in maintaining genome stability during DSB repair.

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