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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-08-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1010349 |
| _version_ | 1811194877659054080 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Michelle M Conti |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T00:34:44Z |
| format | Article |
| id | doaj.art-ee09442a30bf4dfe8cda0546781b70c7 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-12T00:34:44Z |
| publishDate | 2022-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-ee09442a30bf4dfe8cda0546781b70c72022-12-22T03:55:14ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-08-01188e101034910.1371/journal.pgen.1010349Repression of essential cell cycle genes increases cellular fitness.Michelle M ContiJulie M GhizzoniAna Gil-BonaWen WangMichael CostanzoRui LiMackenzie J FlynnLihua Julie ZhuChad L MyersCharles BooneBrenda J AndrewsJennifer A BenantiA 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.https://doi.org/10.1371/journal.pgen.1010349 |
| spellingShingle | 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 Repression of essential cell cycle genes increases cellular fitness. PLoS Genetics |
| 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 |
| url | https://doi.org/10.1371/journal.pgen.1010349 |
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