Polo-like kinases and DNA damage checkpoint: beyond the traditional mitotic functions.
Polo-like kinases (Plks) are a family of serine-threonine kinases that play a pivotal role in cell cycle progression and in cellular response to DNA damage. The Plks are highly conserved from yeast to mammals. There are five Plk family members (Plk1-5) in humans, of which Plk1, is the best characterized. The Plk1 isoform is being aggressively pursued as a target for cancer therapy, following observations that this protein is overexpressed in human tumors and is actively involved in malignant transformation. The roles of Plks in mitotic entry, spindle pole functions and cytokinesis are well established and have been the subject of several recent reviews. In this review, we discuss functions of Plks other than their classical roles in mitotic progression. When cells incur DNA damage, they activate checkpoint mechanisms that result in cell cycle arrest and allow time for repair. If the damage is extensive and cannot be repaired, cells will undergo cell death by apoptosis. If the damage is repaired, cells can resume cycling, as part of the process known as checkpoint recovery. If the damage is not repaired or incompletely repaired, cells can override the checkpoint and resume cycling with damaged DNA, a process called checkpoint adaptation. The Plks play a role in all three outcomes and their involvement in these processes will be the subject of this review.