BRCA2: a universal recombinase regulator
- PMID: 18066084
- DOI: 10.1038/sj.onc.1210870
BRCA2: a universal recombinase regulator
Abstract
Homologous recombination has a dual role in eukaryotic organisms. Firstly, it is responsible for the creation of genetic variability during meiosis by directing the formation of reciprocal crossovers that result in random combinations of alleles and traits. Secondly, in mitotic cells, it maintains the integrity of the genome by promoting the faithful repair of DNA double-strand breaks (DSBs). In vertebrates, it therefore plays a key role in tumour avoidance. Mutations in the tumour suppressor protein BRCA2 are associated with predisposition to breast and ovarian cancers, and loss of BRCA2 function leads to genetic instability. BRCA2 protein interacts directly with the RAD51 recombinase and regulates recombination-mediated DSB repair, accounting for the high levels of spontaneous chromosomal aberrations seen in BRCA2-defective cells. Recent observations indicate that BRCA2 also plays a critical role in meiotic recombination, this time through direct interactions with the meiosis-specific recombinase DMC1. The interactions of BRCA2 with RAD51 and DMC1 lead us to suggest that the BRCA2 tumour suppressor is a universal regulator of recombinase actions.
Similar articles
-
BRCA2 regulates homologous recombination in response to DNA damage: implications for genome stability and carcinogenesis.Cancer Res. 2005 May 15;65(10):4117-25. doi: 10.1158/0008-5472.CAN-04-3071. Cancer Res. 2005. PMID: 15899802
-
BRCA1 regulates RAD51 function in response to DNA damage and suppresses spontaneous sister chromatid replication slippage: implications for sister chromatid cohesion, genome stability, and carcinogenesis.Cancer Res. 2005 Dec 15;65(24):11384-91. doi: 10.1158/0008-5472.CAN-05-2156. Cancer Res. 2005. PMID: 16357146
-
Cancer-associated mutations in BRC domains of BRCA2 affect homologous recombination induced by Rad51.J Mol Biol. 2009 Nov 13;393(5):1007-12. doi: 10.1016/j.jmb.2009.09.011. Epub 2009 Sep 10. J Mol Biol. 2009. PMID: 19747923
-
From meiosis to postmeiotic events: uncovering the molecular roles of the meiosis-specific recombinase Dmc1.FEBS J. 2010 Feb;277(3):590-8. doi: 10.1111/j.1742-4658.2009.07503.x. Epub 2009 Dec 15. FEBS J. 2010. PMID: 20015079 Review.
-
DNA recombination, chromosomal stability and carcinogenesis: insights into the role of BRCA2.DNA Repair (Amst). 2004 Aug-Sep;3(8-9):835-43. doi: 10.1016/j.dnarep.2004.03.008. DNA Repair (Amst). 2004. PMID: 15279768 Review.
Cited by
-
BRCA1 tumor suppressor network: focusing on its tail.Cell Biosci. 2012 Feb 27;2(1):6. doi: 10.1186/2045-3701-2-6. Cell Biosci. 2012. PMID: 22369660 Free PMC article.
-
Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls.BMC Cancer. 2010 Apr 16;10:145. doi: 10.1186/1471-2407-10-145. BMC Cancer. 2010. PMID: 20398395 Free PMC article.
-
Sequence conversion by single strand oligonucleotide donors via non-homologous end joining in mammalian cells.J Biol Chem. 2010 Jul 23;285(30):23198-207. doi: 10.1074/jbc.M110.123844. Epub 2010 May 19. J Biol Chem. 2010. PMID: 20489199 Free PMC article.
-
The Fanconi anemia protein interaction network: casting a wide net.Mutat Res. 2009 Jul 31;668(1-2):27-41. doi: 10.1016/j.mrfmmm.2008.11.018. Epub 2008 Dec 3. Mutat Res. 2009. PMID: 19101576 Free PMC article. Review.
-
Progress and prospects in research and clinical practice of hormone receptor-positive, HER-2-negative breast cancer with BRCA1/2 mutations.Discov Oncol. 2023 Jun 23;14(1):110. doi: 10.1007/s12672-023-00732-0. Discov Oncol. 2023. PMID: 37351713 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous