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. In normal cells, checkpoint responses are a critical safeguard to prevent tumorigenesis promoted by genetic instability. 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[1]. CHK1 is a checkpoint kinase in mammals and regulates G2–M and S-phase cell-cycle checkpoints. 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 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. Although structurally distinct, CHK2 shares overlapping substrate specificity with CHK1. The observations that CHK2 is rapidly activated following exposure to IR or topotecan, whereas CHK1 is markedly activated by agents that interfere with DNA replication, have led to the idea that cell-cycle progression is blocked by CHK1 when replication is inhibited, and by CHK2 when double-strand breaks (DSBs) are present[2].