Although structurally distinct, CHK2 shares overlapping substrate specificity with CHK1. CHK1 is activated by phosphorylation in response to various types of DNA damage in mammals, including damage that is induced by IR, ultraviolet (UV) light, hydroxyurea (HU) and topoisomerase inhibitor. It is expressed in the S and G2 phases of proliferating cells and is absent or expressed at very low levels in quiescent and differentiated cells. CHK1 is a checkpoint kinase in mammals and regulates G2–M and S-phase cell-cycle checkpoints.

Two structurally unrelated but functionally similar protein serine/threonine kinases, checkpoint kinase 1 (CHK1 EC 2.7.11.1) and checkpoint kinase 2 (CHK2), have emerged as the major mediators of cell cycle checkpoints in response to genotoxic stress. In normal cells, checkpoint responses are a critical safeguard to prevent tumorigenesis promoted by genetic instability. Mammalian cells have established highly elaborate surveillance systems to detect DNA damages and other forms of genotoxic stress, which is essential to maintain the genomic integrity and, hence, cellular viability.

What is chk