CHEK2 is the official symbol for the human gene CHK2 checkpoint homolog. It is located on the long (q) arm of chromosome 22.[1][2][3]
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The protein encoded by this gene, CHK2 a protein kinase that is activated in response to DNA damage and is involved in cell cycle arrest.[1]
In response to DNA damage and replication blocks, cell cycle progression is halted through the control of cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1.[4] In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage.[5][6]
A mutation in CHEK2 gene results in decreased DNA-repair, or inability of the cell to undergo apoptosis when it ought to have done so. Thus, a mutation leads to an increased susceptibility to cancer. The following conditions are examples of such cancers.
A deletion-mutation at position 1100 of the CHEK2 gene is associated with an increased risk of breast cancer, particularly in the European population. In women of Northern and Eastern European descent CHEK2*1100delC carrier status confers a 2-3 fold risk of breast cancer. In this ethnic group, women with a familial history of breast cancer have a 4.8 fold risk of breast cancer equal to a lifetime risk of breast cancer of 37%.[7]
The CHEK2*1100delC mutation was originally associated with the Li-Fraumeni syndrome,[8] however the relative high prevalence of the mutation in the general population (0.5%) has made this association unlikely.[9]
CHEK2 has been shown to interact with PLK1,[10] MDC1,[11] MSH2,[12][13] GINS2,[14] PLK3,[15] MUS81[16] and BRCA1.[5][17]
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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