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γH2A/γH2AX Mediates DNA Damage-Specific Control of Checkpoint Signaling in Saccharomyces cerevisiae

Jasmine Siler1, Na Guo1,2, Zhengfeng Liu1

  • 1Department of Biology, University of Rochester, Rochester, NY 14627, USA.

International Journal of Molecular Sciences
|March 13, 2024
PubMed

Insights

Histone H2A phosphorylation (γH2A) negatively regulates DNA damage checkpoints (DDC) in yeast, suppressing cell cycle arrest. This suggests γH2A

Area of Science:

  • Cellular biology
  • Molecular genetics
  • Biochemistry

Background:

  • DNA damage checkpoints (DDC) are crucial for cell cycle arrest and DNA repair.
  • Histone H2A phosphorylation (γH2A) is an early chromatin marker of DNA damage.
  • Previous studies showed varied roles for γH2A in DDC.

Purpose of the Study:

  • To investigate the role of γH2A in DDC signaling in response to specific DNA damaging agents.
  • To elucidate the mechanism by which γH2A influences DDC and DNA repair.

Main Methods:

  • Utilized yeast (*Saccharomyces cerevisiae*) as a model organism.
  • Applied genotoxic agents camptothecin and methyl methanesulfonate.
  • Investigated γH2A's effect on G2/M checkpoint and DDC signaling.
  • Examined the recruitment of DDC and DNA repair factors.

Main Results:

  • γH2A negatively regulates the G2/M checkpoint against camptothecin (a topoisomerase I poison).
  • γH2A suppresses DDC signaling induced by methyl methanesulfonate (an alkylating agent).
  • γH2A mediates competitive recruitment of Rad9 and Rtt107 to DNA lesions.

Conclusions:

  • γH2A exhibits DNA damage-specific effects on DDC signaling.
  • γH2A plays a role in balancing DDC and DNA repair.
  • The function of γH2A in DDC is modulated by the type of DNA damage encountered.
Keywords:
DNA damage checkpointRad53Rad9camptothecinγH2A/γH2AX

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