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Msc1 acts through histone H2A.Z to promote chromosome stability in Schizosaccharomyces pombe

Shakil Ahmed1, Barbara Dul, Xinxing Qiu

  • 1Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, The State University of New Jersey, Piscataway, New Jersey 08854-5635, USA.

Genetics
|October 20, 2007
PubMed

Insights

Msc1 protein promotes chromosome stability and cell survival after DNA damage by interacting with histone H2A.Z. Loss of Msc1 function leads to increased chromosome loss, highlighting its role in DNA repair pathways.

Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • The DNA damage checkpoint pathway is crucial for maintaining genomic integrity.
  • The protein kinase Chk1 plays a central role in mediating cell cycle progression following DNA damage.
  • Msc1 was identified as a suppressor that enhances survival in Chk1-deficient cells exposed to DNA damage.

Purpose of the Study:

  • To investigate the function of Msc1 in DNA damage response and chromosome stability.
  • To elucidate the molecular mechanism by which Msc1 promotes cell survival.
  • To explore the potential role of histone variants in Msc1-mediated processes.

Main Methods:

  • Genetic analysis of msc1 mutants and their interactions with kinetochore components.
  • Phenotypic analysis of chromosome loss rates in msc1 null cells.
  • Investigating the effect of Msc1 on CENP-A localization and suppression of centromere mutants.
  • Assessing the genetic interaction between Msc1 and the histone H2A.Z variant (pht1).

Main Results:

  • Loss of msc1 function results in increased chromosome loss and genetic interactions with kinetochore mutants.
  • Msc1 overexpression suppresses defects in CENP-A, a centromere-specific histone H3 variant.
  • Msc1's function is dependent on the histone H2A.Z variant (pht1), as demonstrated by genetic interactions and suppression studies.
  • Msc1 null cells exhibit compromised CENP-A localization to centromeres.

Conclusions:

  • Msc1 is essential for maintaining chromosome stability and facilitates cell survival following DNA damage.
  • Msc1 likely functions through the histone H2A.Z variant (pht1) to regulate centromere function and chromosome integrity.
  • This study provides the first genetic evidence for histone H2A.Z involvement in centromere function in fission yeast.

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