The central effector of DDR, CHK2, can self-activate when it is overexpressed; self-activation is associated with CHK2 threonine 68 and 387 phosphorylation [15], and CHK2 overexpression can exert counterproductive effects such as in liver cancer leading to spontaneous and trans-phosphorylation events that in turn result in increased mis-segregation of chromosomes, supporting the notion of a concentration-dependent condition in promoting its activation, e.g., CHK2 overexpression identifies a subclass of hepatocellular carcinoma with chromosomal instability [16,17]. This evidence concerns the gene CHEK2 and hepatocellular carcinoma.