TITLE:
Effect of the R406H Substitution on the Normal Function of CHEK2
AUTHORS:
Ahmet Yilmaz, Michael E. Davis, Weiqiang Zhao
KEYWORDS:
Breast Cancer; CHEK2; Yeast; R406H; French-Canadian Women; Indian Women
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.5 No.4,
March
12,
2014
ABSTRACT: CHEK2 (Checkpoint kinase homolog 2) encodes a
protein involved in pathways that arrest the cell cycle in response to genomic
stress such as DNA damage or replication blocks. Carriers of some of the CHEK2 mutations are at an increased risk
of breast cancer. A mutation in the kinase domain of the CHEK2 gene resulting in the R406H substitution has been reported.
However, it is currently unknown whether the substitution alters the function
of CHEK2 in vitro. We evaluated the
effect of the R406H substitution on the normal function of CHEK2 using a yeast
complementation assay. The yeast cells lacking Rad53, the yeast homologue of human CHEK2 were transformed with the wild type as well as plasmids
carrying mutations resulting in the R406H, 1100delC, and S428F variants. Yeast
cells carrying the R406H variant grew at a rate similar to those carrying the
wild type CHEK2, whereas the yeast carrying the S428F and 1100delC mutants grew
at a slower rate. These results suggest that, unlike the well-known pathogenic
alleles such as 1100delC and S428F, the R406H substitution does not abrogate
the function of CHEK2. Therefore, this variant is probably not important in
development of breast cancer in women.