Replication stress by MMS stimulates DNA synthesis in post-replicative G2-phase in S. pombe

Seong Min Kim1, Susan L Forsburg1

  • 1University of Southern California, Los Angeles, California, United States.

PubMed

Insights

Fission yeast cells activate DNA synthesis in G2-phase when exposed to DNA damage. Degrading the Mcm4 helicase during G2 prevents this post-replicative DNA synthesis, highlighting its role in DNA repair.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • DNA replication typically occurs during S-phase.
  • Replication stress can induce DNA synthesis outside of S-phase.
  • Mitotic DNA synthesis and G2 DNA synthesis pathways are activated to maintain genomic stability.

Purpose of the Study:

  • To investigate DNA synthesis in G2 and M phases in response to DNA alkylating agents.
  • To determine the role of DNA replication helicase Mcm4 in G2-phase DNA synthesis.

Main Methods:

  • Treatment of fission yeast with methyl methanesulfonate (MMS).
  • Auxin-inducible degradation of Mcm4 during G2 and M phases.
  • Analysis of DNA synthesis in G2 and M phases.

Main Results:

  • Fission yeast cells stimulate DNA synthesis in G2 but not M-phase following MMS treatment.
  • Auxin-induced degradation of Mcm4 during G2 inhibits post-replicative DNA synthesis.
  • Mcm4 degradation during mitosis does not affect DNA synthesis.

Conclusions:

  • DNA synthesis is activated in G2-phase of fission yeast in response to DNA alkylating agents.
  • The DNA replication helicase Mcm4 is crucial for G2-phase post-replicative DNA synthesis.
  • Mcm4's role in DNA synthesis is specific to G2 and not M-phase.

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