Regulation of polo-like kinase 1 by DNA damage in mitosis: Inhibition of mitotic PLK-1 by protein phosphatase 2A

DNA damage triggers multiple checkpoint pathways to arrest cell cycle progression. Polo-like kinase 1 (Plk1) is an important regulator of several events during mitosis. In addition to Plk1 functions in cell cycle, Plk1 is involved in DNA damage checkpoint in G₂ phase. Normally, ataxia telangiectasia-mutated kinase (ATM) is a key enzyme involved in G₂ phase cell cycle arrest following DNA damage, and inhibition of Plk1 by DNA damage during G₂ occurs in a ATM/ATR-dependent manner. However, it is still unclear how Plk1 is regulated in response to DNA damage in mitosis in which Plk1 is already activated. Here, we show that treatment of mitotic cells with doxorubicin and β-irradiation inhibits Plk1 activity through dephosphorylation of Plk1, and cells were arrested in G₂ phase. Treatments of the phosphatase inhibitors and siRNA experiments suggested that PP2A pathway might be involved in regulating mitotic Plk1 activity in mitotic DNA damage. Finally, we propose a novel pathway, which is connected between ATM/ATR/Chk and protein phosphatase-Plk1 in DNA damage response in mitosis.