Investigation effect of common mutations of BRCA۱ in breast cancer on protein structure: Bioinformatical Approach

چکیده مقاله

Breast cancer is the most common cancer in the female population. BRCA1 and BRCA2 are the most important genes which were proposed for inherited breast cancer. These genes belong to the tumor suppressor gene family for their capacity to repair damaged DNA through a process known as DNA double-strand break repair. Mutations in these genes increased rate of breast and ovarian cancers about 59-87%. BRCA1 is most often mutated in three domains: the N-terminal RING domain, exons 11-13, and the BRCT domain. Mutations in different area of BRCA1 gene increased the risk of familial breast cancer, changed protein function and developed risk of cancers. Nowadays over 70 different mutations in BRCA1 gene have been identified in Iranian breast cancer patients. About 10 of these mutations are the most common recurrent mutations. The aim of this study was to investigate effect of common mutations of BRCA1 on protein structure. At first we chose BRCA1 structures from proteins data bank (PDB) then by using different softwares, we have analyzed the effect of some common mutations on the secondary and 3D structures of protein. It was found mutations can cause changes in the angles Phi, Psi and Omega in secondary structure, and some of these mutations are effective on the tertiary structure. For example, mutation 5213 G˃A in exon 20, which alters the glycine 1738 amino acid to glutamate, effects on changed in the tertiary structure of proteins.