A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair

Weizhe Li, Hong Yan Wang, Xiaolu Zhao, Hongguo Duan, Binghua Cheng, Yafei Liu, Mengjie Zhao, Wenjie Shu, Yuchao Mei, Zengqi Wen, Mingliang Tang, Lin Guo, Guohong Li, Qiang Chen, Xiaoqi Liu, Hai Ning Du

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43 Scopus citations


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.

Original languageEnglish
Article numbereaau7566
JournalScience advances
Issue number3
StatePublished - 2019

Bibliographical note

Funding Information:
We thank H. Pei (Georgetown University) for the HeLa/RFP-H2B cell line; J. Huang (Zhejiang University) for NBS1-GFP and GFP-CtIP plasmids and the -RAD51 antibody; L. Zheng, Min Wu, H. Liu, and Y. Wang (Wuhan University) for reagents and technical support; and B. Zhu (Institute of Biophysics, Chinese Academy of Sciences), C. Zhang (University of Southern California), J. Li (Capital Normal University), and J. Wong (Huadong Normal University) for the constructive suggestion. This work was supported by the National Natural Science Foundation of China (31770843, 31271369, and 31870827) and Major State Basic Research Development Program of China (2013CB910700).

Publisher Copyright:
Copyright © 2019 The Authors, some rights reserved.

ASJC Scopus subject areas

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