Mutations in DNA damage response genes and breast cancer susceptibility

Excerpt

The risk of breast cancer is greatly increased in women who carry a mutation in one of the breast cancer susceptibility genes BRCA1 or 2. In the years since these genes were first isolated, evidence of their function in DNA damage responses and the DNA repair mechanism has accumulated. The DNA damage resulting from ionising and UV irradiation activates the ataxia-telangiectasia-mutated (ATM) and ataxia-telangiectasia- and RAD3-related (ATR) protein kinases, which in turn leads to the phosphorylation of BRCA proteins and other downstream targets such as CHEK2. It is known that the BRCA1 and 2 and CHEK2 gene products are cellular proteins that function to sense DNA damage, and to activate genes that both prevent cell cycle progression and initiate the DNA repair process. Several articles published over the last year have broadened our understanding of this pathway and its relevance to breast cancer risk and development. …