Specifically, DNA damage-activated phosphatidylinositol kinase family protein (PIKK) ATM phosphorylates site Thr68 and activates CHK2.

Furthermore, CHK2 is known to phosphorylate the cell-cycle transcription factor E2F1 and the promyelocytic leukemia protein (PML) involved in apoptosis (programmed cell death).

[7] Bell et al. (1999) discovered three CHEK2 germline mutations among four Li–Fraumeni syndrome (LFS) and 18 Li–Fraumeni-like (LFL) families.

[8] Beyond initial speculations, screening of LFS and LFL patients has revealed no or very rare individual missense variants in the CHEK2 gene.

Most notably, the deletion of a single DNA nucleotide at position 1100 in exon 10 (1100delC) produces a nonfunctional version of the CHK2 protein, truncated at the kinase domain.

The loss of normal CHK2 protein function leads to unregulated cell division, accumulated damage to DNA and in many cases, tumor development.

Studies link the mutation to cases of prostate, lung, colon, kidney, and thyroid cancers.

[12] CHEK2 regulates cell cycle progression and spindle assembly during mouse oocyte maturation and early embryo development.

The response of oocytes to DNA double-strand break damage involves a pathway hierarchy in which ATR kinase signals to CHEK2 which then activates p53 and p63 proteins.

[16] CHEK2 has been shown to interact with: This article incorporates text from the United States National Library of Medicine, which is in the public domain.