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A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair
Polo-like kinase 1 (Plk1) is a crucial regulator of cell cycle progression; but the mechanism of regulation of Plk1 activity is not well understood. We present evidence that Plk1 activity is controlled by a balanced methylation and phosphorylation switch. The methyltransferase G9a monomethylates Plk...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402851/ https://www.ncbi.nlm.nih.gov/pubmed/30854428 http://dx.doi.org/10.1126/sciadv.aau7566 |
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author | Li, Weizhe Wang, Hong-Yan Zhao, Xiaolu Duan, Hongguo Cheng, Binghua Liu, Yafei Zhao, Mengjie Shu, Wenjie Mei, Yuchao Wen, Zengqi Tang, Mingliang Guo, Lin Li, Guohong Chen, Qiang Liu, Xiaoqi Du, Hai-Ning |
author_facet | Li, Weizhe Wang, Hong-Yan Zhao, Xiaolu Duan, Hongguo Cheng, Binghua Liu, Yafei Zhao, Mengjie Shu, Wenjie Mei, Yuchao Wen, Zengqi Tang, Mingliang Guo, Lin Li, Guohong Chen, Qiang Liu, Xiaoqi Du, Hai-Ning |
author_sort | Li, Weizhe |
collection | PubMed |
description | Polo-like kinase 1 (Plk1) is a crucial regulator of cell cycle progression; but the mechanism of regulation of Plk1 activity is not well understood. We present evidence that Plk1 activity is controlled by a balanced methylation and phosphorylation switch. The methyltransferase G9a monomethylates Plk1 at Lys209, which antagonizes phosphorylation of T210 to inhibit Plk1 activity. We found that the methyl-deficient Plk1 mutant K209A affects DNA replication, whereas the methyl-mimetic Plk1 mutant K209M prolongs metaphase-to-anaphase duration through the inability of sister chromatids separation. We detected accumulation of Plk1 K209me1 when cells were challenged with DNA damage stresses. Ablation of K209me1 delays the timely removal of RPA2 and RAD51 from DNA damage sites, indicating the critical role of K209me1 in guiding the machinery of DNA damage repair. Thus, our study highlights the importance of a methylation-phosphorylation switch of Plk1 in determining its kinase activity and functioning in DNA damage repair. |
format | Online Article Text |
id | pubmed-6402851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-64028512019-03-08 A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair Li, Weizhe Wang, Hong-Yan Zhao, Xiaolu Duan, Hongguo Cheng, Binghua Liu, Yafei Zhao, Mengjie Shu, Wenjie Mei, Yuchao Wen, Zengqi Tang, Mingliang Guo, Lin Li, Guohong Chen, Qiang Liu, Xiaoqi Du, Hai-Ning Sci Adv Research Articles Polo-like kinase 1 (Plk1) is a crucial regulator of cell cycle progression; but the mechanism of regulation of Plk1 activity is not well understood. We present evidence that Plk1 activity is controlled by a balanced methylation and phosphorylation switch. The methyltransferase G9a monomethylates Plk1 at Lys209, which antagonizes phosphorylation of T210 to inhibit Plk1 activity. We found that the methyl-deficient Plk1 mutant K209A affects DNA replication, whereas the methyl-mimetic Plk1 mutant K209M prolongs metaphase-to-anaphase duration through the inability of sister chromatids separation. We detected accumulation of Plk1 K209me1 when cells were challenged with DNA damage stresses. Ablation of K209me1 delays the timely removal of RPA2 and RAD51 from DNA damage sites, indicating the critical role of K209me1 in guiding the machinery of DNA damage repair. Thus, our study highlights the importance of a methylation-phosphorylation switch of Plk1 in determining its kinase activity and functioning in DNA damage repair. American Association for the Advancement of Science 2019-03-06 /pmc/articles/PMC6402851/ /pubmed/30854428 http://dx.doi.org/10.1126/sciadv.aau7566 Text en Copyright © 2019 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 Li, Weizhe Wang, Hong-Yan Zhao, Xiaolu Duan, Hongguo Cheng, Binghua Liu, Yafei Zhao, Mengjie Shu, Wenjie Mei, Yuchao Wen, Zengqi Tang, Mingliang Guo, Lin Li, Guohong Chen, Qiang Liu, Xiaoqi Du, Hai-Ning A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair |
title | A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair |
title_full | A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair |
title_fullStr | A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair |
title_full_unstemmed | A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair |
title_short | A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair |
title_sort | methylation-phosphorylation switch determines plk1 kinase activity and function in dna damage repair |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402851/ https://www.ncbi.nlm.nih.gov/pubmed/30854428 http://dx.doi.org/10.1126/sciadv.aau7566 |
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