The Role of chk2 in Response to DNA Damage in Cancer Cells

Abstract

Accumulation of gene changes and chromosomal instability in response to cellular DNA damage lead to cancer. DNA damage induces cell cycle checkpoints pathways. Checkpoints regulate DNA replication and cell cycle progression, chromatin restructuring, and apoptosis. Checkpoint kinase 2 (chk2) is activated in response to DNA lesions. ATM phosphorylate chk2. The activated Chk2 kinase can phosphorylate the substrates, including the Cdc25 phosphatases, p53, PML, E2F-1, and Brca1, which has been associated with DNA repair, cell cycle arrest or induction of apoptosis. Also, Chk2 is a tumor suppressor gene that maintains genomic integrity and it has been suggested as an anticancer therapy target.