The subcellular localization and physiological function of this gene is greatly modulated by the several alternately splices isoforms that are found. Several of these alternatively spliced transcript variants have been described, however, not all have had their full-length natures identified.

According to Entrez-Gene, BRCA1 gene maps to NC_000017.9 in the region between 38449840 and 38530994 on the minus strand and spans across 81.1 kilo bases. According to Spidey (mRNA to genomic sequence alignment tool, http://www.ncbi.nlm.nih.gov/spidey), BRCA1 has 24 exons, the sizes being 181, 99, 54, 78, 89, 140, 105, 47, 77, 89, 172, 127, 191, 311, 88, 78, 41, 84, 55, 74, 61, 1506.

BRCA1 mRNA NM_007302.3 has 7388bps. The BRCA1 gene contains two separate promoters that induce transcription of mRNAs with different 5 UTRs, a shorter 5UTRa and a longer 5UTRb. The downregulation of BRCA1 gene expression in certain breast cancers is caused by a switch from expression of a 5UTRa, which enables efficient translation, to expression of 5 UTRb, which contains secondary structure and upstream open reading frames that strongly inhibit translation.

According to Entrez Gene the BRCA1 pseudogene 1 (BRCA1P1) is located on 17q21.

BRCA1 sequence is not well conserved between mammals, however, two domains, the C terminal BRCT (BRCA1 C Terminal) motifs and the N-terminal RING domain are highly conserved.

BRCA1 is an 1863 amino acid 220kDa protein with an E3 ubiquitin ligase activity as well as a phospho-peptide binding activity. It has several domains that are essential for its function as depicted in the figure. The RING finger domain of BRCA1, commonly found in many DNA repair proteins, consists of a conserved core of approximately 50 amino acids in a pattern of seven cysteine residues and one histidine residue to form a structure that can bind to two Zn++ ions. This motif aids in mediating protein-protein interaction, as exemplified by the interaction of BRCA1 with BARD1 (BRCA1 associated RING domain). This interaction is critical since mutations in the Zn++ binding regions, crucial for heterodimerization with BARD1, have been found in tumours. BRCA1 accumulates in distinct foci in the nucleus during S phase and this transfer is aided by its Nuclear Localisation Signal (NLS) domain. A further role of BARD1 is also implicated whereby its association with the RING finger domain of BRCA1 is necessary for the transfer of BRCA1 to the nucleus. BRCA1 interacts with Rad50 of the MRN complex through the region AA 341-748 and can directly bind to branched, flap and four way DNA structures through a central domain spanning residues 452-1079. The protein inhibits the nucleolytic activities of the Mre11/Rad50/Nbs1 complex as a result of this direct DNA binding. The C terminus of BRCA1, which can function as a transcriptional activation domain, consists of two tandemly arranged elements called BRCT (BRCA1 C- terminal). This motif specifically binds to phosphorylated proteins, an event that is commonly associated with DNA damage response. BRCA1 is capable of interacting directly with BRCA2 and with Rad51 via BRCA2 through this motif. Another protein that interacts with BRCA1 via BRCT is the BRCA1 associated C-terminal helicase ( BACH1 ). BACH1 is said to aid BRCA1 in the DNA damage response and maintain the protein at the nuclear foci formed after DNA damage response. Other proteins that can interact with BRCA1 through the BRCT domains are C terminal Interacting protein /CtIP), RNA Polymerase II, BACH 1 (a member of DEAH helicase family) and p53 .

BRCA1 is ubiquitously expressed in humans with the highest levels observed in the ovaries, testis and thymus. It is a tumour suppressor and a reduced expression is correlated with the transformation procedure and aetiology of sporadic breast cancer. This reduction is expression is said to be transcriptionally regulated with implications of aberrant promoter methylation at CpG dinucleotides as well as CREB binding sites.

Located in the nucleus.

Role of BRCA1 in DNA repair: BRCA1 is a part of a large complex of proteins, the BASC, which monitors the genome for damage and signals downstream effectors. BRCA1 has been implicated in two pathways of DNA double strand break repair: homologous recombination (HR) and non homologous end joining (NHEJ). Upon exposure to DNA damaging agents, BRCA1 becomes hyperphosphorylated and is rapidly relocated, along with Rad51, to sites of DNA synthesis marked by proliferating cell nuclear antigen (PCNA). Rad51, a homolog of the bacterial RecA, is a central player in HR, catalyzing the invasion of the single stranded DNA in a homologous duplex and facilitating the homology search during the establishment of joint molecules. A recent study, however, has indicated that BRCA1 deficient breast cancer cells compensate for this deficiency by upregulating Rad51. The resultant HR may be erroneous and thereby lead to tumorigenesis. In addition, BRCA1 is said to inhibit the MRN complex which is is implicated in bringing together two DNA strands together for the error prone NHEJ. BRCA1-deficient cells are sensitive to ionizing radiation and DNA damaging drugs, such as mitomycin C.
Transcriptional regulation: BRCA1 is capable of transcriptional regulation and chromatin remodelling when tethered to promoters of genes important in the DNA repair process and breast cancer markers. It is a member of the core RNA polymerase II transcriptional machinery, a feature exploited by the DNA damage recognition process. In addition, BRCA1 interacts with p300/CBP, transcriptional coactivators for CREB. p300/CBP are inhibited by the viral oncoprotein E1A and the functionality of E1A as an oncogene could be in part caused by an obstruction of BRCA1:p300/CBP cooperation resulting in the loss of the tumour-suppressing function of BRCA1. BRCA1 can act as a transcriptional coactivator or co repressor of proteins implicated in chromatin remodelling, such as the histone deacetylase complexes or components of the SWI/SNF-related chromatin-remodelling complex.
Cell Cycle Regulation by BRCA1: BRCA1, based on its phosphorylation status, elicits DNA damage induced cell cycle arrest at several stages through modulation of specific downstream target genes. BRCA1 transactivates p21cip1/WAF1, which contributes to an arrest at the G1/S boundary. ATM phosphorylation of BRCA1 appears to be important for its role in the intra S phase checkpoint activation. BRCA1 is also implicated in the transcriptional regulation of several genes such as cyclinB, 14-3-3sigma, GADD45, wee-1 kinase and PLK1 associated with the G2/M checkpoint.
p53-dependent apoptosis: The BRCA1 protein is capable of physically interacting with the p53 tumour suppressor gene, and can stimulate p53-dependent transcription from the p21WAF1/CIP1 mdm2 and promoters. In addition, the BRCA1-BARD1 complex is required for the phosphorylation of p53 at Ser15 by ATM/ATR following DNA damage by IR or UV radiation. The phosphorylation of p53 at Ser-15 is essential for the G(1)/S cell cycle arrest via transcriptional induction of the cyclin-dependent kinase inhibitor p21 after DNA damage.
Ubiquitination: BRCA1 and BARD1 interact together to form an E3 ubiquitin ligase. RNA polII stalled at sites of DNA damage is a target for this ubiquitin ligase mediated degradation following DNA damage, thereby allowing access to the repair machinery. BRCA1 ubiquitinates the transcriptional preinitiation complex, not for proteasomal degradation, but to prevent a stable association of TFIIE and TFIIH; thereby blocking the initiation of mRNA synthesis.

Dog (Canis familiaris): BRCA1
Chimpanzee(Pan troglodytes): BRCA1
Rat (Rattus norvegicus): Brca1
Mouse(Mus musculus): Brca1
Chicken(Gallus gallus): BRCA1

BRCA1 germline mutations contribute significantly to the development of familial/hereditary breast and ovarian cancer. However, each gene carries as many as 1000 different disease associated mutations, many of which are rare. These mutations are distributed uniformly along the entire coding region and intronic sequences flanking each exon. The mutations are at a high penetrance therefore women who carry these mutations have a lifetime risk of 80-90% to develop breast cancer. Founder mutations such as the BRCA1-185delAG and 5382insC are found among Ashkenazi Jews. Larger and complex genomic rearrangements in the exons 21 and 22 of the BRCA1 gene, resulting in a lack of the BRCT motif have been reported.