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Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the S-phase DNA damage checkpoint

Nicholas Willis1, Nicholas Rhind

  • 1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Molecular Biology of the Cell
|November 28, 2008
PubMed

Insights

The S-phase DNA damage checkpoint slows replication. Restraining recombination via proteins like Mus81 and Rqh1 is crucial for this DNA damage response in fission yeast.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • The S-phase DNA damage checkpoint is vital for genome stability during replication.
  • Cds1 is a key effector kinase in fission yeast's S-phase checkpoint, regulating replication slowing.
  • Replication stress triggers checkpoint activation to prevent catastrophic DNA damage.

Purpose of the Study:

  • To identify downstream effectors of Cds1 involved in replication slowing.
  • To elucidate the roles of Mus81 and Rqh1 in the S-phase DNA damage checkpoint.
  • To define the epistatic relationships between Mus81, Rqh1, and Rhp51 in DNA damage response.

Main Methods:

  • Utilized cds1Delta mutants of Schizosaccharomyces pombe treated with methyl methane sulfonate.
  • Investigated the genetic interactions between mus81, rqh1, and rhp51 mutants.
  • Analyzed replication slowing defects and recombination pathways.

Main Results:

  • Identified Mus81 (endonuclease) and Rqh1 (helicase) as downstream of Cds1, essential for checkpoint-dependent replication slowing.
  • Demonstrated that Mus81 acts epistatically to Rhp51, which acts epistatically to Rqh1.
  • Showed that Rhp51 removal suppresses rqh1Delta slowing defects but not mus81Delta defects.

Conclusions:

  • Mus81 and Rqh1 are critical components of the S-phase DNA damage checkpoint pathway.
  • Restraining homologous recombination is a necessary mechanism for slowing replication under DNA damage stress.
  • This study defines a novel pathway involving recombination regulation in S-phase checkpoint control.

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