The Impact of XRCC3 Thr241Met Polymorphism on Incidence of Breast Cancer; a Bioinformatics Study

Breast cancer is the leading malignancy in women and caused by a combination of genetic and environmental factors. X-ray repair cross complementing group 3 (XRCC3) protein is involved in single strand DNA break rejoining and double-strand DNA break rejoining. To date, 3 different polymorphisms of XRCC3 have been found in the population. It has been reported that XRCC3 Thr241Met polymorphism, affected the enzyme function and/or its interaction with other proteins involved in DNA damage and repair. Many studies indicated that this polymorphism might be associated with increased risks of a number of human cancers including breast cancer. The protein is part of the CX3 complex consisting of RAD51C and XRCC3. The complex is involved in homologous recombination repair. In order to investigate the impact of Thr241Met polymorphism on interaction of XRCC3 and RAD51C proteins, initially FASTA sequences of these two proteins were taken from www.uniprot.org database and modeling of XRCC3, RAD51C and XRCC3 Thr241Met proteins were performed by SWISS-MODEL server. Then, the interaction of RAD51C protein with XRCC3 and XRCC3 Thr241Met proteins was studied by PRISM server and binding energies were obtained. The results showed that the energy of binding to RAD51C for the Thr241Met polymorphism decreases about 20%. This result confirms previous results which show association of Thr241Met polymorphism with the risk of breast cancer. As a conclusion of these studies, increase in the rate of breast cancer’s incidence in individuals who carry XRCC3 Thr241Met polymorphism, probably can be resulted from decrease in binding energy of XRCC3 and RAD51C proteins.

Keywords:

Breast cancer , XRCC3 , polymorphism , PRISM , protein-protein interaction