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Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle–specific activation of homologous recombination
Homologous recombination is exquisitely activated only during specific cell phases. In the G(1) phase, homologous recombination activity is completely suppressed. According to previous reports, the activation of homologous recombination during specific cell phases depends on the kinase activity of c...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007264/ https://www.ncbi.nlm.nih.gov/pubmed/32083180 http://dx.doi.org/10.1126/sciadv.aay2669 |
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author | Lim, Gyubum Chang, Yeonji Huh, Won-Ki |
author_facet | Lim, Gyubum Chang, Yeonji Huh, Won-Ki |
author_sort | Lim, Gyubum |
collection | PubMed |
description | Homologous recombination is exquisitely activated only during specific cell phases. In the G(1) phase, homologous recombination activity is completely suppressed. According to previous reports, the activation of homologous recombination during specific cell phases depends on the kinase activity of cyclin-dependent kinase 1 (CDK1). However, the precise regulatory mechanism and target substrates of CDK1 for this regulation have not been completely determined. Here, we report that the budding yeast CDK1, Cdc28, phosphorylates the major homologous recombination regulators Rad51 and Rad52. This phosphorylation occurs in the G(2)/M phase by Cdc28 in combination with G(2)/M phase cyclins. Nonphosphorylatable mutations in Rad51 and Rad52 impair the DNA binding affinity of Rad51 and the affinity between Rad52 rings that leads to their interaction. Collectively, our data provide detailed insights into the regulatory mechanism of cell cycle–dependent homologous recombination activation in eukaryotic cells. |
format | Online Article Text |
id | pubmed-7007264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-70072642020-02-20 Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle–specific activation of homologous recombination Lim, Gyubum Chang, Yeonji Huh, Won-Ki Sci Adv Research Articles Homologous recombination is exquisitely activated only during specific cell phases. In the G(1) phase, homologous recombination activity is completely suppressed. According to previous reports, the activation of homologous recombination during specific cell phases depends on the kinase activity of cyclin-dependent kinase 1 (CDK1). However, the precise regulatory mechanism and target substrates of CDK1 for this regulation have not been completely determined. Here, we report that the budding yeast CDK1, Cdc28, phosphorylates the major homologous recombination regulators Rad51 and Rad52. This phosphorylation occurs in the G(2)/M phase by Cdc28 in combination with G(2)/M phase cyclins. Nonphosphorylatable mutations in Rad51 and Rad52 impair the DNA binding affinity of Rad51 and the affinity between Rad52 rings that leads to their interaction. Collectively, our data provide detailed insights into the regulatory mechanism of cell cycle–dependent homologous recombination activation in eukaryotic cells. American Association for the Advancement of Science 2020-02-07 /pmc/articles/PMC7007264/ /pubmed/32083180 http://dx.doi.org/10.1126/sciadv.aay2669 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Lim, Gyubum Chang, Yeonji Huh, Won-Ki Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle–specific activation of homologous recombination |
title | Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle–specific activation of homologous recombination |
title_full | Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle–specific activation of homologous recombination |
title_fullStr | Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle–specific activation of homologous recombination |
title_full_unstemmed | Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle–specific activation of homologous recombination |
title_short | Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle–specific activation of homologous recombination |
title_sort | phosphoregulation of rad51/rad52 by cdk1 functions as a molecular switch for cell cycle–specific activation of homologous recombination |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007264/ https://www.ncbi.nlm.nih.gov/pubmed/32083180 http://dx.doi.org/10.1126/sciadv.aay2669 |
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