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BRCA1, which functions as a tumor suppressor in human breast cancer cells, is a nuclear phosphoprotein which associates with RNA polymerase II holoenzyme. Mutations in BRCA1 are predicted to be responsible for approximately 45% of inherited breast cancer and more than 80% of inherited breast and ovarian cancer. BRCA1 may function as a transcriptional regulator, due to an amino terminal DNA-binding ring finger motif, nuclear localization signals, and an acidic carboxy terminal domain. BRCA1 is also a granin-like protein that functions as a secreted growth inhibitory protein. BRCA1 may normally serve as a negative regulator of mammary epithelial cell growth. This function is compromised in breast cancer either by direct mutation or by alterations in gene expression. BRCA1 participates in transcription-coupled repair of oxidative DNA damage. BRCA1 spans an 81-kb region of human chromosome 17, and consists of 24 exons, 22 of which are coding exons. The BRCA1 genomic sequence has an unusually high density of Alu repetitive DNA (41.5%), but a relatively low density (4.8%) of other repetitive sequences. BRCA1 intron lengths ranged in size from 403 bp to 9.2 kb and contain 3 intragenic microsatellite markers located in introns 12, 19, and 20. Other genes have been localized close to BRCA1 on chromosome 17. The order of genes on the chromosome is: centromere-IFP35-VAT1-RHO7-BRCA1-M17S2-telomere. Alternative splicing may play a significant role in modulating the subcellular localization and physiological function of BRCA1.
Source: Entrez Gene.

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