'Cell cycle checkpoint kinase 2 (CHEK2) is a transducer of cellular responses to DNA damage. The CHEK2 1100delC has previously been shown to be a low-penetrance breast cancer susceptibility allele. We have evaluated the role of another CHEK2 variant, I157T in the FHA domain of the gene, for association with ... More
Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2.
AuthorsLi J, Williams BL, Haire LF, Goldberg M, Wilker E, Durocher D, Yaffe MB, Jackson SP, Smerdon SJ
JournalMol Cell
PubMed ID12049740
'The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in vitro selected ... More
Linkage of ATM to cell cycle regulation by the Chk2 protein kinase.
AuthorsMatsuoka S, Huang M, Elledge SJ
JournalScience
PubMed ID9836640
In response to DNA damage and replication blocks, cells prevent cell cycle progression through the control of critical cell cycle regulators. We identified Chk2, the mammalian homolog of the Saccharomyces cerevisiae Rad53 and Schizosaccharomyces pombe Cds1 protein kinases required for the DNA damage and replication checkpoints. Chk2 was rapidly phosphorylated ... More
Alternative splicing and mutation status of CHEK2 in stage III breast cancer.
The DNA damage checkpoint kinase, CHK2, promotes growth arrest or apoptosis through phosphorylating targets such as Cdc25A, Cdc25C, BRCA1, and p53. Both germline and somatic loss-of-function CHEK2 mutations occur in human tumours, the former linked to the Li-Fraumeni syndrome, and the latter found in diverse types of sporadic malignancies. Here ... More