Repression of essential cell cycle genes increases cellular fitness

Michelle M. Conti, Julie M. Ghizzoni, Ana Gil-Bona, Wen Wang, Michael Costanzo, Rui Li, Mackenzie J. Flynn, Lihua Julie Zhu, Chad L. Myers, Charles Boone, Brenda J. Andrews, Jennifer A. Benanti

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

A network of transcription factors (TFs) coordinates transcription with cell cycle events in eukaryotes. Most TFs in the network are phosphorylated by cyclin-dependent kinase (CDK), which limits their activities during the cell cycle. Here, we investigate the physiological consequences of disrupting CDK regulation of the paralogous repressors Yhp1 and Yox1 in yeast. Blocking Yhp1/Yox1 phosphorylation increases their levels and decreases expression of essential cell cycle regulatory genes which, unexpectedly, increases cellular fitness in optimal growth conditions. Using synthetic genetic interaction screens, we find that Yhp1/Yox1 mutations improve the fitness of mutants with mitotic defects, including condensin mutants. Blocking Yhp1/Yox1 phosphorylation simultaneously accelerates the G1/S transition and delays mitotic exit, without decreasing proliferation rate. This mitotic delay partially reverses the chromosome segregation defect of condensin mutants, potentially explaining their increased fitness when combined with Yhp1/Yox1 phosphomutants. These findings reveal how altering expression of cell cycle genes leads to a redistribution of cell cycle timing and confers a fitness advantage to cells.

Original languageEnglish (US)
Article numbere1010349
JournalPLoS genetics
Volume18
Issue number8
DOIs
StatePublished - Aug 29 2022

Bibliographical note

Publisher Copyright:
Copyright: © 2022 Conti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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