TY - JOUR
T1 - A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair
AU - Li, Weizhe
AU - Wang, Hong Yan
AU - Zhao, Xiaolu
AU - Duan, Hongguo
AU - Cheng, Binghua
AU - Liu, Yafei
AU - Zhao, Mengjie
AU - Shu, Wenjie
AU - Mei, Yuchao
AU - Wen, Zengqi
AU - Tang, Mingliang
AU - Guo, Lin
AU - Li, Guohong
AU - Chen, Qiang
AU - Liu, Xiaoqi
AU - Du, Hai Ning
N1 - Publisher Copyright:
Copyright © 2019 The Authors, some rights reserved.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1126/sciadv.aau7566
DO - 10.1126/sciadv.aau7566
M3 - Article
C2 - 30854428
AN - SCOPUS:85062699998
VL - 5
JO - Science advances
JF - Science advances
IS - 3
M1 - eaau7566
ER -