Yox1 links MBF-dependent transcription to completion of DNA synthesis

Area of Science:

• Cell biology
• Molecular biology
• Genetics

Background:

• Cells activate a DNA synthesis checkpoint when replication is challenged, halting cell cycle progression.
• In fission yeast, Cds1 kinase manages this checkpoint, inhibiting M-phase entry and stabilizing replication forks.
• The mechanism by which Cds1 triggers S-phase gene transcription remains largely unknown.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying the transcriptional activation of S-phase genes during the DNA synthesis checkpoint.
• To identify novel interactors of the Mlu1 binding factor (MBF) complex, a key regulator of S-phase gene transcription.

Main Methods:

• Purification of novel interactors of the MBF complex.
• Identification of the repressor Yox1 as an MBF interactor.
• Phosphorylation analysis of Yox1 during checkpoint activation.

Main Results:

• Yox1 was identified as a repressor that interacts with the MBF complex.
• Upon DNA synthesis checkpoint activation, Yox1 undergoes phosphorylation.
• Phosphorylation of Yox1 abrogates its binding to the MBF complex.

Conclusions:

• The inactivation of the repressor Yox1 through phosphorylation is a key mechanism for activating S-phase gene transcription during the DNA synthesis checkpoint.
• This process ensures that essential S-phase genes remain transcribed until replication defects are resolved.
• The findings provide new insights into cell cycle regulation and DNA damage response pathways.