Chk2 (checkpoint kinase 2) is the mammalian homolog of the Saccharomyces cerevisiae Rad53 and is required for the DNA damage and replication checkpoints. In response to low-dose ionizing radiation (IR), which occurs in an ataxia telangiectasia mutated (ATM)-dependent manner, Chk2 can phosphorylate the mitosis-inducing phosphatase Cdc25C on an inhibitory site, blocking entry into mitosis, and p53 on a regulatory site, causing G1 arrest (2,3). In human tissues, Chk2 is homogeneously expressed in renewing cell populations such as epidermis or intestine, heterogeneous in conditionally renewing tissues, and absent or at low level in static tissues such as muscle or brain. Mutations in Chk2 inactivates DNA damage checkpoint pathway involving Chk2 in lung cancer suggesting that reduced expression of Chk2 may be responsible for the development of lung cancer. The Chk2-/- knockout cells are resistant to DNA damage-induced apoptosis, defective for p53 stabilization and for induction of p53-dependent transcripts such as p21 in response to gamma irradiation. CHK2 is a serine/threonine kinase in the CDS subfamily that is activated in response to DNA damage and may regulate cell cycle arrest. It is the human homolog of RAD53 in S. cerevisiae and CDS1 in S. pombe. The protein has a FHA domain, which means it is located in the nucleus. Its kinase activity is up regulated by autophosphorylation in response to DNA damage and to replication blocks. It controls cell cycle checkpoint and may participate in transduction of the DNA damage and replicational stress signals. It also inhibits CDC25 phosphatase to prevent the cell entry into mitosis. Studies show that the deficiency of CHK2 may cause Li-Fraumeni syndrome and other human cancers, such as breast cancer via other gene’s function.
							
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