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Repression of essential cell cycle genes increases cellular fitness
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462756/ https://www.ncbi.nlm.nih.gov/pubmed/36037231 http://dx.doi.org/10.1371/journal.pgen.1010349 |
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author | Conti, Michelle M. Ghizzoni, Julie M. Gil-Bona, Ana Wang, Wen Costanzo, Michael Li, Rui Flynn, Mackenzie J. Zhu, Lihua Julie Myers, Chad L. Boone, Charles Andrews, Brenda J. Benanti, Jennifer A. |
author_facet | Conti, Michelle M. Ghizzoni, Julie M. Gil-Bona, Ana Wang, Wen Costanzo, Michael Li, Rui Flynn, Mackenzie J. Zhu, Lihua Julie Myers, Chad L. Boone, Charles Andrews, Brenda J. Benanti, Jennifer A. |
author_sort | Conti, Michelle M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9462756 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-94627562022-09-10 Repression of essential cell cycle genes increases cellular fitness Conti, Michelle M. Ghizzoni, Julie M. Gil-Bona, Ana Wang, Wen Costanzo, Michael Li, Rui Flynn, Mackenzie J. Zhu, Lihua Julie Myers, Chad L. Boone, Charles Andrews, Brenda J. Benanti, Jennifer A. PLoS Genet Research Article 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. Public Library of Science 2022-08-29 /pmc/articles/PMC9462756/ /pubmed/36037231 http://dx.doi.org/10.1371/journal.pgen.1010349 Text en © 2022 Conti et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Conti, Michelle M. Ghizzoni, Julie M. Gil-Bona, Ana Wang, Wen Costanzo, Michael Li, Rui Flynn, Mackenzie J. Zhu, Lihua Julie Myers, Chad L. Boone, Charles Andrews, Brenda J. Benanti, Jennifer A. Repression of essential cell cycle genes increases cellular fitness |
title | Repression of essential cell cycle genes increases cellular fitness |
title_full | Repression of essential cell cycle genes increases cellular fitness |
title_fullStr | Repression of essential cell cycle genes increases cellular fitness |
title_full_unstemmed | Repression of essential cell cycle genes increases cellular fitness |
title_short | Repression of essential cell cycle genes increases cellular fitness |
title_sort | repression of essential cell cycle genes increases cellular fitness |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462756/ https://www.ncbi.nlm.nih.gov/pubmed/36037231 http://dx.doi.org/10.1371/journal.pgen.1010349 |
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