The cell cycle is regulated by multiple checkpoints that determine cell fate. Such checkpoints ensure that DNA replication and chromosomal segregation are completed with high fidelity. When DNA is damaged, specific kinases and phosphatases, key components of cell cycle checkpoints, function to arrest the cell cycle and provide the necessary time for DNA repair. For example, DNA damage induces arrest of the cell cycle at the G2 checkpoint via Wee1-mediated inhibitory phosphorylation of the kinase Cdc2. Inhibition is relieved by the Cdc25C phosphatase via Cdc2 dephosphorylation. In turn, the Chk1 and Chk2 protein kinases phosphorylate and inhibit Cdc25C, thus preventing activation of the Cdc2-cyclin B complex and entry into mitosis. Chk2, the human homolog of S. cerevisiae Rad53 and S. pombe Cds1, contains a C-terminal kinase domain, an N-terminal regulatory region that is rich in TQ and SQ pairs, and a forked head-associated domain (FHA) which is found in other cell cycle kinases. Chk2 is expressed during late G1 to M phase and is found in the nucleoplasm. Thus, Chk1 and Chk2 activity may be an important checkpoint that inhibits entry into mitosis in response to DNA damage.
This antibody is routinely tested by western blot analysis. Other applications were tested at BD Biosciences Pharmingen during antibody development only or reported in the literature.