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The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor

Tsvetomira Ivanova1, Isabel Alves-Rodrigues, Blanca Gómez-Escoda

  • 1Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, Barcelona 08003, Spain Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115.

Molecular Biology of the Cell
|September 6, 2013
PubMed

Insights

Fission yeast proteins Yox1 and Cdc10 link cell cycle regulation to DNA checkpoints. Phosphorylation of Cdc10 by Chk1 inactivates MluI-binding factor (MBF) transcription, crucial for DNA damage survival.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The DNA replication checkpoint in fission yeast involves Cds1 kinase.
  • Cds1 inactivates the repressor Yox1, activating MluI-binding factor (MBF)-dependent transcription for DNA synthesis.
  • This process is vital for G1-to-S phase transition.

Purpose of the Study:

  • To investigate the role of Cdc10 in the DNA damage checkpoint.
  • To determine how DNA damage signaling affects MBF-dependent transcription.
  • To elucidate the integration of cell cycle regulation and checkpoint pathways.

Main Methods:

  • Utilizing fission yeast as a model organism.
  • Employing DNA-damaging agents to activate the DNA damage checkpoint.
  • Analyzing protein phosphorylation events using Chk1 kinase.
  • Assessing the impact on MluI-binding factor (MBF) binding to chromatin.

Main Results:

  • Cdc10, a component of the MBF complex, is phosphorylated by Chk1 upon DNA damage.
  • This phosphorylation leads to the release of MBF from chromatin, repressing MBF-dependent transcription.
  • The inactivation of MBF is critical for cell survival under DNA-damaging conditions.

Conclusions:

  • Yox1 and Cdc10 act as key regulators, integrating normal cell cycle progression with DNA replication and DNA damage checkpoints.
  • These proteins form a unified transcriptional complex that responds to distinct cellular stresses.
  • The findings highlight a conserved mechanism for maintaining genomic integrity and cell viability.

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