Cell cycle events are regulated by the sequential activation and deactivation of cyclin dependent kinases (Cdks) and by proteolysis of cyclins. Chk1 and Chk2 are involved in these processes as regulators of Cdks. Chk2 is the mammalian orthologue of the budding yeast Rad53 and fission yeast Cds1 checkpoint kinases. The amino-terminal domain of Chk2 contains a series of seven serine or threonine residueseach followed by glutamine (SQ or TQ motif). Phosphorylation at Thr68 is a prerequisite for the subsequent activation step, which is attributable to autophosphorylation of Chk2 at residues Thr383 and Thr387 in the activation loop of the kinase domain.