Breast Cancer 1 Early Onset Gene Analysis

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Breast cancer is one of the most common and important diseases that affect women and ovarian cancer is the fourth most common cause of cancer mortality in American women1. These cancers are triggered by germline mutations on the C-terminal of a gene called BRCA1 (or “Breast Cancer 1, Early Onset Gene”) tumor suppressor. The BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, consists of 24 exons and encodes a multidomain protein of 1863 amino acid residues in human2. The BRCA1 proteins produced from BRCA1 gene help preventing cells from growing and dividing too rapidly or in an uncontrolled way3. The family of BRCA1 genes is called RING-type zinc fingers or RNF. The BRCA1 protein is characterized within the superfamily of Rad9-like proteins which consist of C-terminal BRCT repeats that assist in the binding of phosphorylated proteins in the DNA damage response and DNA repair4. Like many other genes involved in familial cancer, BRCA1 appears to encode a tumor suppressor, a protein that acts as a negative regulator of tumor growth1. BRCA1 proteins are important in genomic stability so loss of their function can cause genetic instability which lead to tumourigenesis. Thus, the sequence of BRCA1 protein is analyzed to the understanding the protein’s function in the development of the cancers.
The sequence of BRCA1 protein shows that there are quite a few of cysteine residues. These cysteine residues form disulfide bonds which help stabilize the secondary structure of the protein. The secondary structure of BRCA1 protein indicates that there are alpha helices and beta turns which are connected by loops and turns. The 3D structure of BRCA1/BARD1 RING-domain heterodimer is shown in figure 1.

Figure 1...

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... Thus, the loss of BRCA1 can result in defective DNA damage repair, abnormal centrosome duplication, cell-cycle arrest, growth retardation, increased apoptosis, genetic instability and tumorigenesis2. The study of BRCA1 mutation in mice may be used for new therapeutic approaches, although the cause of the mutation in BRCA gene is unclear.
Women who inherit a mutation in one copy of BRCA1 or BRCA2 are at high risk of developing breast and ovarian cancers6. This could be due to the disruption in the pathway of BRCA proteins in the cell nucleus. If BRCA1 is defective, it loses its ability to fix damaged DNA and causes tumor. It is because once the defective BRCA1 raises, it allows the cells to develop and divide uncontrollably. Since defective in BRCA1 causes cancers, it is important to understanding the function of the protein by analyzing its sequence and structure.

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