To control or to be controlled? Dual roles of CDK2 in DNA damage and DNA damage response.

CDK2 (cyclin-dependent kinase 2), a member of the CDK family, has been shown to play a role in many cellular activities including cell cycle progression, apoptosis and senescence. Recently, accumulating evidence indicates that CDK2 is involved in DNA damage and DNA repair response (DDR). When DNA is damaged by internal or external genotoxic stresses, CDK2 activity is required for proper DNA repair in vivo and in vitro, whereas inactivation of CDK2 by siRNA techniques or by inhibitors could result in DNA damage and stimulate DDR. Hence, CDK2 seems to play dual roles in DNA damage and DDR. On one aspect, it is activated and stimulates DDR to repair DNA damage when DNA damage occurs; on the other hand, its inactivation directly leads to DNA damage and evokes DDR. Here, we describe the roles of CDK2 in DNA damage and DDR, and discuss the potential application of CDK2 inhibitors as anti-cancer agents.