Spreading the signal: Dissociation of Chk1 from chromatin

Abstract

The effector kinase Chk1 plays a critical role in the DNA damage checkpoint response by phosphorylating regulators of the cell cycle machinery, resulting in an inhibition of cell cycle progression. In the presence of genotoxic stress, the PI3 kinase-like kinase ATR rapidly phosphorylates Chk1 on conserved serine residues, thereby triggering kinase activation through the release of an auto-inhibitory region present at its C-terminus and by regulating interactions with other proteins. Recent data have demonstrated an additional regulatory mechanism of Chk1 functioning: Chk1 binds chromatin in unperturbed cells and dissociates from chromatin in response to DNA damage in a manner that is dependent on PIKK-mediated phosphorylation. Here, I give an overview of these findings and discuss the implications of these data for our understanding of the execution of the checkpoint arrest induced after the detection of DNA damage. ©2006 Landes Bioscience.