Repression of essential cell cycle genes increases cellular fitness

Related Experiment Video

Updated: Aug 30, 2025

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

27.6K

Michelle M Conti1, Julie M Ghizzoni1, Ana Gil-Bona1

  • 1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America.

Plos Genetics
|August 29, 2022
PubMed

Insights

Disrupting cyclin-dependent kinase (CDK) regulation of Yhp1/Yox1 transcription factors in yeast unexpectedly boosts cellular fitness. This occurs by altering cell cycle gene expression, improving mitotic defects and conferring a fitness advantage.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Transcription factors (TFs) coordinate gene expression with the cell cycle in eukaryotes.
  • Cyclin-dependent kinases (CDKs) regulate TF activity via phosphorylation, limiting their function during cell cycle progression.

Purpose of the Study:

  • To investigate the physiological effects of disrupting CDK regulation on paralogous yeast repressors Yhp1 and Yox1.
  • To understand how altered TF activity impacts cell cycle gene expression and cellular fitness.

Main Methods:

  • Investigated yeast Yhp1 and Yox1 phosphoregulation.
  • Performed synthetic genetic interaction screens.
  • Analyzed cell cycle progression and gene expression.

Main Results:

  • Blocking Yhp1/Yox1 phosphorylation increased their levels and decreased cell cycle gene expression, unexpectedly enhancing fitness under optimal conditions.
  • Yhp1/Yox1 mutations improved the fitness of mutants with mitotic defects, such as condensin mutants.
  • Phosphorylation disruption accelerated G1/S transition and delayed mitotic exit without reducing proliferation, partially reversing condensin mutant chromosome segregation defects.

Conclusions:

  • Altering cell cycle gene expression through modified TF regulation redistributes cell cycle timing.
  • This redistribution confers a fitness advantage, particularly in cells with pre-existing mitotic challenges.

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