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Effect of the r406h Substitution on the Normal Function of ChEK2

Advances in Bioscience and Biotechnology 2014年第4期5卷 386-392页

作者： Ahmet Yilmaz Michael E. Davis Weiqiang Zhao Department of Animal Sciences The Ohio State University Columbus USA Department of human Genetics McGill University Montreal Canada The Lady Davis Institute Jewish General Hospital Montreal Canada Department of Pathology The Ohio State Univer-sity Columbus USA

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.

关键词： Breast Cancer ChEK2 Yeast r406h French-Canadian Women Indian Women

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