Science Advances · 2019 · 76 citations · 29 references
Life SciencesCell BiologyMolecular BiologyDna RepairDna ReplicationEpigeneticsCell Cycle ControlCell-cycle CheckpointsCell-cycle RegulationDna DamageDna Double-strand Break RepairReplication Checkpoint ControlDna Damage Checkpoint ActivationDna Damage Checkpoint KinasesDna Damage Checkpoint SignalingDna Damage Repair PathwaysDna Damage Response PathwaysDna Damage ResponsesDna Double-strand Break Repair SignalingMetaphase Arrest
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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Makoto Tachibana, Kenji Sugimoto, Tatsunobu Fukushima et al. · Journal of Biological Chemistry · 2001 · 775 citations · Full text
Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery
Libor Macůrek, Arne Lindqvist, Dan Lim et al. · Nature · 2008 · 711 citations
Polo-like kinase-1 is a target of the DNA damage checkpoint
Veronique A. J. Smits, Rob Klompmaker, Lionel Arnaud et al. · Nature Cell Biology · 2000 · 436 citations