title: Claspin: timing the cell cycle arrest when the genome is damaged.
abstract: DNA damage checkpoints maintain genomic integrity by delaying cell cycle progression in response to genotoxic stress and stalled replication forks. One central pathway in the checkpoint response is the ATR-Chk1 pathway, in which, upon DNA damage, ATR phosphorylates and activates the effector kinase Chk1. This process depends on the adaptor protein Claspin that bridges ATR and Chk1. Once the damage is repaired, this pathway must somehow be switched off to allow the cell to continue the cell division process, an event known as checkpoint recovery. Polo-like kinase 1 (Plk1) plays a central role during checkpoint recovery. Interestingly, the Xenopus homologue of Plk1, Plx1, is able to bind and phosphorylate Claspin, releasing it from DNA and thereby contributing to Chk1 inactivation. Moreover, it was recently demonstrated that Claspin levels are controlled by proteasomal degradation, and this is regulated by Plk1. Importantly, Plk1-mediated proteosomal degradation of Claspin appears to be essential for check-point recovery. Here we review these recent findings and discuss the mechanisms of checkpoint regulation by Claspin.
authors.affiliation: Unidad de Investigación, Hospital Universitario de Canarias, Tenerife, Spain. rfreire@ull.es
authors.forename: Raimundo
authors.initials: R
authors.lastname: Freire
authors.forename: Marcel A T M
authors.initials: MA
authors.lastname: van Vugt
authors.forename: Ivan
authors.initials: I
authors.lastname: Mamely
authors.forename: René H
authors.initials: RH
authors.lastname: Medema
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D004249:DNA Damage; D016678:Genome / Q000235:genetics*; D008954:Models, Biological; D014981:Xenopus / Q000235:genetics; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C416368:CLSPN protein, Xenopus; D029867:Xenopus Proteins