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The role of specific checkpoint-induced S-phase transcripts in resistance to replicative stress

Chaitali Dutta1, Nicholas Rhind

  • 1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

Plos One
|September 15, 2009
PubMed

Insights

Fission yeast DNA replication checkpoints maintain S-phase transcription by regulating MBF. This transcriptional regulation, alongside cell-cycle arrest and fork stabilization, is crucial for cell survival during replication stress.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Genetics

Background:

  • DNA replication is essential for cell division.
  • Replication stress can arise from DNA damage or replication fork stalling.
  • Cellular checkpoints are critical for maintaining genomic stability during replication stress.

Purpose of the Study:

  • To investigate the role of transcriptional regulation in response to replication stress.
  • To compare the contributions of transcriptional regulation, cell-cycle arrest, and fork stabilization to replication-stress resistance.
  • To elucidate the specific roles of mik1 and mrc1 transcripts in the DNA replication checkpoint.

Main Methods:

  • Utilized fission yeast as a model organism.
  • Investigated checkpoint kinase Cds1 and its regulation of MBF (S-phase transcription factor).
  • Assessed the impact of transcriptional regulation on replication-stress resistance and cell survival.

Main Results:

  • Checkpoint activation during S phase modulates transcription, maintaining the normal S-phase transcriptional program.
  • Transcriptional regulation provides modest resistance compared to fork stabilization but significantly contributes to cell survival.
  • Identified specific roles for mik1 and mrc1 transcripts in the checkpoint response.

Conclusions:

  • Checkpoint regulation of G1/S transcription is vital for responding to replicative stress.
  • Transcriptional control is a significant factor in cell survival under replication stress conditions.
  • Mik1 and Mrc1 play important roles in the DNA replication checkpoint mechanism.

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