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Breast cancer type 1 susceptibility protein

Location of the genes BRCA1 and BRCA2 on chromosomes 13 and 17

Symbol(s): BRCA1
Other names:RING finger protein 53, Breast cancer 1 Early Onset, PSCP, RNF53
Genetic data
Locus: Chr. 17 q21
Protein Structure/Function
Protein length: 1863 (Amino Acids)
Molecular Weight: 207732 (Da)
Functions: DNA repair, Tumor suppressor, Transcription regulator, Centrosome dynamics
Domains: RING domain, 2 BRCT domains
Motifs: 2 NLS motifs, 2 NES motifs, CC motif
Taxa expressing:Homo sapiens
Cell types:many; ovaries, testis, mammary glands, lymphocyte, prostate, cervix
Subcellular localization:Primary: Nucleus; Secondary: Cytoplasm, Centrosome
Medical/Biotechnological data
Diseases:breast-ovarian cancer (BOC) Online 'Mendelian Inheritance in Man' (OMIM) 113705
Database Links
Codes: EntrezGene 672, RefSeq NM_007295, UniProt P38398, Online 'Mendelian Inheritance in Man' (OMIM) 113705

BRCA1 (breast cancer 1, early onset) is a human gene that belongs to a class of genes known as tumor suppressors, which maintains genomic integrity to prevent uncontrolled proliferation. The multifactorial BRCA1 protein product is involved in DNA damage repair, ubiquitination, transcriptional regulation as well as other functions. Variations in the gene have been implicated in a number of hereditary cancers, namely breast, ovarian and prostate. The BRCA1 gene is located on the long (q) arm of chromosome 17 at band 21, from base pair 38,449,843 to base pair 38,530,933 (map).


Function and mechanism

The BRCA1 protein is directly involved in the repair of damaged DNA. In the nucleus of many types of normal cells, the BRCA1 protein is thought to interact with RAD51 to mend breaks in DNA, though the details and significance of this interaction is the subject of debate.[1] These breaks can be caused by natural radiation or other exposures, but also occur when chromosomes exchange genetic material in preparation for cell division. The BRCA2 protein, which has a function similar to that of BRCA1, also interacts with the RAD51 protein. By repairing DNA, these three proteins play a role in maintaining the stability of the human genome.

Research suggests that both the BRCA1 and BRCA2 proteins regulate the activity of other genes and play a critical role in embryo development. The BRCA1 protein probably interacts with many other proteins, including tumor suppressors and regulators of the cell division cycle.

Mutations & Cancer Risk

Certain variations of the BRCA1 gene lead to an increased risk for breast cancer. Researchers have identified more than 600 mutations in the BRCA1 gene, many of which are associated with an increased risk of cancer.

These mutations can be changes in one or a small number of DNA base pairs (the building blocks of DNA). Those mutations can be identified with PCR and sequencing.

In some cases, large segments of DNA are rearranged. Those large segments, also called large rearrangements, can be a deletion or a duplication of one or several exons in the gene. Classical methods for mutations detection(sequencing) are unable to reveal those mutations.[2]. Other methods are proposed : Q-PCR[3], Multiplex Ligation-dependent Probe Amplification (MLPA)[4] , and Quantitative Multiplex PCR of Shorts Fluorescents Fragments (QMPSF)[5] . New methods have been recently proposed : heteroduplex analysis (HDA) by multi-capillary electrophoresis or also dedicated oligonucleotides array based on comparative genomic hybridization (array-CGH)[6] .

A mutated BRCA1 gene usually makes a protein that does not function properly because it is abnormally short. Researchers believe that the defective BRCA1 protein is unable to help fix mutations that occur in other genes. These defects accumulate and may allow cells to grow and divide uncontrollably to form a tumor.

In addition to breast cancer, mutations in the BRCA1 gene also increase the risk on ovarian, Fallopian tube, prostate and colon cancers. Moreover, precancerous lesions (dysplasia) within the Fallopian tube have been linked to BRCA1 gene mutations.

See also

  • BRCA2
  • Breast cancer
  • Mary-Claire King

BRCA1 gene was discovered in 1994, by studying Mormon families in Utah, and that was done via linkage analysis.


  1. ^ S.J. Boulton (2006). "Cellular functions of the BRCA tumour-suppressor proteins". Biochemical Society Transactions 34 (5): 633-645. PMID 17052168.
  2. ^ Mazoyer S. (2005). "Genomic rearrangements in the BRCA1 and BRCA2 genes". Hum Mutat. 25 (5): 415-22. PMID: 15832305.
  3. ^ Barrois M. et al (2004). "Real-time PCR-based gene dosage assay for detecting BRCA1 rearrangements in breast-ovarian cancer families". Clin Genet. 65 (2): 131-6. PMID: 14984472.
  4. ^ Hogervorst FB. et al (2003). "Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method". Cancer Res. 63 (7): 1449-53. PMID: 12670888.
  5. ^ Casilli F. et al (2002). "Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragments". Hum Mutat. 20 (3): 218-26. PMID: 12203994.
  6. ^ Rouleau E. et al (2007). "High-resolution oligonucleotide array-CGH applied to the detection and characterization of large rearrangements in the hereditary breast cancer gene BRCA1". Clin Genet. 72 (3): 199-207. PMID: 17718857.

Further reading

  • Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjakoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF (2003). "Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies". Am J Hum Genet 72 (5): 1117-30. PMID 12677558.
  • Barnett GL, Friedrich CA (2004). "Recent developments in ovarian cancer genetics". Curr Opin Obstet Gynecol 16 (1): 79-85. PMID 15128012.
  • Daniel DC (2002). "Highlight: BRCA1 and BRCA2 proteins in breast cancer". Microsc Res Tech 59 (1): 68-83. PMID 12242698.
  • Ding SL, Sheu LF, Yu JC, Yang TL, Chen BF, Leu FJ, Shen CY (2004). "Abnormality of the DNA double-strand-break checkpoint/repair genes, ATM, BRCA1 and TP53, in breast cancer is related to tumour grade". Br J Cancer 90 (10): 1995-2001. PMID 15138484.
  • Foulkes WD, Metcalfe K, Sun P, Hanna WM, Lynch HT, Ghadirian P, Tung N, Olopade OI, Weber BL, McLennan J, Olivotto IA, Begin LR, Narod SA (2004). "Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type". Clin Cancer Res 10 (6): 2029-34. PMID 15041722.
  • Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King MC (1990). "Linkage of early-onset familial breast cancer to chromosome 17q21". Science 250 (4988): 1684-89. PMID 2270482.
  • Liede A, Karlan BY, Narod SA (2004). "Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature". J Clin Oncol 22 (4): 735-42. PMID 14966099.
  • Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, Olopade OI, Eisen A, Weber B, McLennan J, Sun P, Foulkes WD, Narod SA (2004). "Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers". J Clin Oncol 22 (12): 2328-35. PMID 15197194.
  • Parthasarathy, Shobita (2007). Building Genetic Medicine: Breast Cancer, Technology, and the Comparative Politics of Health Care. The MIT Press. ISBN 978-0-262-016242-5. 
  • Powell SN, Kachnic LA (2003). "Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation". Oncogene 22 (37): 5784-91. PMID 12947386.
  • Scully R, Puget N (2002). "BRCA1 and BRCA2 in hereditary breast cancer". Biochimie 84 (1): 95-102. PMID 11900881.
  • Tutt A, Ashworth A (2002). "The relationship between the roles of BRCA genes in DNA repair and cancer predisposition". Trends Mol Med 8 (12): 571-6. PMID 12470990.
  • Venkitaraman AR (2002). "Cancer susceptibility and the functions of BRCA1 and BRCA2". Cell 108 (2): 171-82. PMID 11832208.
  • Zweemer RP, van Diest PJ, Verheijen RH, Ryan A, Gille JJ, Sijmons RH, Jacobs IJ, Menko FH, Kenemans P (2000). "Molecular evidence linking primary cancer of the fallopian tube to BRCA1 germline mutations". gynecol oncol 76 (1). PMID: 10620440.
  • Piek JM, van Diest PJ, Zweemer RP, Jansen JW, Poort-Keesom RJ, Menko FH, Gille JJ, Jongsma AP, Pals G, Kenemans P, Verheijen RH (2001). "Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer". J Pathol. 195 (4). PMID: 11745677.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "BRCA1". A list of authors is available in Wikipedia.
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