Significance of the RING domain of the BRCA1 gene - Review of Missense Mutations
DOI:
https://doi.org/10.58445/rars.2991Keywords:
BRCA 1, BARD 1, RING Domain, E3 ligase, missense mutationsAbstract
Breast cancer occurs around the world, and 2022 data reveal 2,308,897 new breast cancer cases accounted for 11.6% of all new cancer cases (Bray et al., 2024). Breast cancer susceptibility gene 1 (BRCA1) is one of the most common tumor suppressor genes and is detected in at least 5% of patients with breast cancer (Morris et al., 2006). BRCA1 gene mutations are prevalent and found in 35% of the hereditary breast cancer cases. Out of the three domains of the BRCA1 gene, the mutations in the RING domain near the N terminus are reviewed here. Out of the 27 mutations indicated in the RING domain, 14 missense mutations identified with a pathogenic outcome were selected for this review (Gracia et al., 2024). A missense mutation replaces the nucleotide in the gene that affects the protein folding when that gene is expressed, affecting the protein function. The BRCA1 protein forms a heterodimer with the BARD1 protein to perform E3 ligase activity. The RING region of BRCA1 is crucial for heterodimer formation. Suppose a mutation were to occur in the RING region, it might interfere with the two proteins binding to form a heterodimer, thus affecting E3 ligase activity that is crucial for gene regulation through the ubiquitination process. Missense mutations have been shown to have a pathogenic outcome and are therefore studied in detail.
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