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BRCA2 (Breast Cancer Type 2 susceptibility protein) is a human gene1 that is involved in the repair of chromosomal damage and belongs to a class of genes known as tumor suppressor genes.23 Tumor suppressor genes regulate the cycle of cell division by keeping cells from growing and dividing too rapidly or in an uncontrolled way.
The BRCA2 gene is located on the long (q) arm of chromosome 13 at position 12.3 (13q12.3), from base pair 31,787,616 to base pair 31,871,804.1
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Structure and function
Although the structures of the BRCA1 and BRCA2 genes are very different, their functions appear to be similar. The proteins made by both genes are essential for repairing damaged DNA. The BRCA2 protein binds to and regulates the protein produced by the RAD51 gene to fix breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, but also occur when chromosomes exchange genetic material during a special type of cell division that creates sperm and eggs (meiosis). The BRCA1 protein also interacts with the RAD51 protein. By repairing DNA, these three proteins play a role in maintaining the stability of the human genome.
Like BRCA1, BRCA2 probably regulates the activity of other genes and plays a critical role in embryo development.
Related conditions
Certain variations of the BRCA2 gene cause an increased risk for breast cancer. Researchers have identified about 450 mutations in the BRCA2 gene, many of which cause an increased risk of cancer. BRCA2 mutations are usually insertions or deletions of a small number of DNA base pairs (the building material of chromosomes) in the gene. As a result of these mutations, the protein product of the BRCA2 gene is abnormally short and does not function properly. Researchers believe that the defective BRCA2 protein is unable to help fix mutations that occur in other genes. As a result, mutations build up and can cause cells to divide in an uncontrolled way and form a tumor.
People who have two mutated copies of the BRCA2 gene have one type of Fanconi anemia. This condition is caused by extremely reduced levels of the BRCA2 protein in cells, which allows the accumulation of damaged DNA. Patients with Fanconi anemia are prone to several types of leukemia (a type of blood cell cancer); solid tumors, particularly of the head, neck, skin, and reproductive organs; and bone marrow suppression (reduced blood cell production that leads to anemia).
In addition to breast cancer in men and women, mutations in BRCA2 also lead to an increased risk of ovarian, Fallopian tube, prostate, and pancreatic cancers, as well as malignant melanoma. In some studies, mutations in the central part of the gene have been associated with a higher risk of ovarian cancer and a lower risk of prostate cancer than mutations in other parts of the gene. Several other types of cancer have also been seen in certain families with BRCA2 mutations.
Discovery of BRCA2
The BRCA2 gene was discovered in 1995 by Professor Michael Stratton and Dr Richard Wooster (Institute of Cancer Research, UK). The Wellcome Trust Sanger Institute (Hinxton, Cambs, UK) collaborated with Stratton and Wooster to isolate the gene. In honour of this discovery and collaboration, the Wellcome Trust has participated in the construction of a cycle path between Addenbrooke's Hospital site in Cambridge and the nearby village of Great Shelford. It is decorated with over 10,000 lines of 4 colours representing the nucleotide sequence of BRCA2. It makes-up part of the National Cycle Network route 11, and can be seen from the Cambridge-London Liverpool Street train.
See also
References
- ^ a b Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D, et al. (September 1994). "Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13". Science (New York, N.Y.) 265 (5181): 2088–90. doi:. PMID 8091231.
- ^ Duncan JA, Reeves JR, Cooke TG (October 1998). "BRCA1 and BRCA2 proteins: roles in health and disease". Molecular pathology : MP 51 (5): 237–47. PMID 10193517. PMC: 395646, http://mp.bmj.com/cgi/content/abstract/51/5/237.
- ^ Yoshida K, Miki Y (November 2004). "Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage". Cancer science 95 (11): 866–71. doi:. PMID 15546503, http://www.jca.gr.jp/cs/95/11/866.pdf.
Further reading
- Zou JP, Hirose Y, Siddique H, Rao VN, Reddy ES (1999). "Structure and expression of variant BRCA2a lacking the transactivation domain". Oncology reports 6 (2): 437–40. PMID 10023017.
- Venkitaraman AR (2001). "Chromosome stability, DNA recombination and the BRCA2 tumour suppressor". Curr. Opin. Cell Biol. 13 (3): 338–43. doi:. PMID 11343905.
- Orelli BJ, Bishop DK (2001). "BRCA2 and homologous recombination". Breast Cancer Res. 3 (5): 294–8. doi:. PMID 11597317.
- Daniel DC (2002). "Highlight: BRCA1 and BRCA2 proteins in breast cancer". Microsc. Res. Tech. 59 (1): 68–83. doi:. PMID 12242698.
- Tutt A, Ashworth A (2003). "The relationship between the roles of BRCA genes in DNA repair and cancer predisposition". Trends in molecular medicine 8 (12): 571–6. doi:. PMID 12470990.
- Gonçalves A, Viens P, Sobol H, et al. (2005). "[Molecular alterations in breast cancer: clinical implications and new analytical tools]". La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne 26 (6): 470–8. doi:. PMID 15936476.
- Hay T, Clarke AR (2005). "DNA damage hypersensitivity in cells lacking BRCA2: a review of in vitro and in vivo data". Biochem. Soc. Trans. 33 (Pt 4): 715–7. doi:. PMID 16042582.
- Domchek SM, Weber BL (2006). "Clinical management of BRCA1 and BRCA2 mutation carriers". Oncogene 25 (43): 5825–31. doi:. PMID 16998496.
- Honrado E, Osorio A, Palacios J, Benitez J (2006). "Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations". Oncogene 25 (43): 5837–45. doi:. PMID 16998498.
External links
- MeSH BRCA2 Protein
- EntrezGene 675
- GeneCard
- Cancer.gov
- "FORCE: Facing Our Risk of Cancer Empowered -- Hereditary, Genetic Breast or Ovarian Cancer and BRCA Issues". Facing Our Risk of Cancer Empowered, Inc.. Retrieved on 2008-10-11.
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- This page was last modified on 16 October 2008, at 04:47.
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