Editing BRCA2 (section)

==Meiosis==

In the plant ''[[Arabidopsis thaliana]]'', loss of the ''BRCA2'' homolog ''AtBRCA2'' causes severe defects in both male [[meiosis]] and in the development of the female [[gametocyte]].<ref name=Seeliger>{{cite journal |vauthors=Seeliger K, Dukowic-Schulze S, Wurz-Wildersinn R, Pacher M, Puchta H |title=BRCA2 is a mediator of RAD51- and DMC1-facilitated homologous recombination in Arabidopsis thaliana |journal=New Phytol. |volume=193 |issue=2 |pages=364–75 |year=2012 |pmid=22077663 |doi=10.1111/j.1469-8137.2011.03947.x |doi-access=free }}</ref>  AtBRCA2 protein is required for proper localization of the [[synaptonemal complex]] protein AtZYP1 and the recombinases AtRAD51 and AtDMC1.  Furthermore, AtBRCA2 is required for proper meiotic synapsis.  Thus AtBRCA2 is likely important for meiotic recombination.  It appears that AtBRCA2 acts during meiosis to control the single-strand invasion steps mediated by AtRAD51 and AtDMC1 occurring during meiotic [[homologous recombination]]al repair of DNA damages.<ref name=Seeliger />

Homologs of BRCA2 are also essential for meiosis in the fungus ''[[Ustilago maydis]]'',<ref name="pmid12408834">{{cite journal |vauthors=Kojic M, Kostrub CF, Buchman AR, Holloman WK |title=BRCA2 homolog required for proficiency in DNA repair, recombination, and genome stability in Ustilago maydis |journal=Mol. Cell |volume=10 |issue=3 |pages=683–91 |year=2002 |pmid=12408834 |doi= 10.1016/s1097-2765(02)00632-9|doi-access=free }}</ref> the worm ''[[Caenorhabditis elegans]]'',<ref name="pmid18779660">{{cite journal |vauthors=Ko E, Lee J, Lee H |title=Essential role of brc-2 in chromosome integrity of germ cells in C. elegans |journal=Mol. Cells |volume=26 |issue=6 |pages=590–4 |year=2008 |doi=10.1016/S1016-8478(23)14041-6 |pmid=18779660 |doi-access=free }}</ref><ref name="pmid15798199">{{cite journal |vauthors=Martin JS, Winkelmann N, Petalcorin MI, McIlwraith MJ, Boulton SJ |title=RAD-51-dependent and -independent roles of a Caenorhabditis elegans BRCA2-related protein during DNA double-strand break repair |journal=Mol. Cell. Biol. |volume=25 |issue=8 |pages=3127–39 |year=2005 |pmid=15798199 |pmc=1069622 |doi=10.1128/MCB.25.8.3127-3139.2005 }}</ref> and the fruitfly ''[[Drosophila melanogaster]]''.<ref name="pmid18266476">{{cite journal |vauthors=Klovstad M, Abdu U, Schüpbach T |title=Drosophila brca2 is required for mitotic and meiotic DNA repair and efficient activation of the meiotic recombination checkpoint |journal=PLOS Genet. |volume=4 |issue=2 |pages=e31 |year=2008 |pmid=18266476 |pmc=2233675 |doi=10.1371/journal.pgen.0040031 |doi-access=free }}</ref>

Mice that produce truncated versions of BRCA2 are viable but sterile.<ref name="pmid9398843">{{cite journal |vauthors=Connor F, Bertwistle D, Mee PJ, Ross GM, Swift S, Grigorieva E, Tybulewicz VL, Ashworth A |title=Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation |journal=Nat. Genet. |volume=17 |issue=4 |pages=423–30 |year=1997 |pmid=9398843 |doi=10.1038/ng1297-423 |s2cid=42462448 }}</ref>  BRCA2 mutant rats have a phenotype of growth inhibition and sterility in both sexes.<ref name="pmid16964288">{{cite journal |vauthors=Cotroneo MS, Haag JD, Zan Y, Lopez CC, Thuwajit P, Petukhova GV, Camerini-Otero RD, Gendron-Fitzpatrick A, Griep AE, Murphy CJ, Dubielzig RR, Gould MN |title=Characterizing a rat Brca2 knockout model |journal=Oncogene |volume=26 |issue=11 |pages=1626–35 |year=2007 |pmid=16964288 |doi=10.1038/sj.onc.1209960 |doi-access=free }}</ref>  Aspermatogenesis in these mutant rats is due to a failure of homologous chromosome synapsis during meiosis.

===BRC repeat sequences===

''[[DMC1 (gene)|DMC1]]'' (DNA meiotic recombinase 1) is a [[meiosis]] specific homolog of ''[[RAD51]]'' that mediates strand exchange during [[homologous recombination]]al repair.  DMC1 promotes the formation of DNA strand invasion products (joint molecules) between homologous DNA molecules.  Human DMC1 interacts directly with each of a series of repeat sequences in the BRCA2 protein (called BRC repeats) that stimulate joint molecule formation by DMC1.<ref name=Martinez>{{cite journal |vauthors=Martinez JS, von Nicolai C, Kim T, Ehlén Å, Mazin AV, Kowalczykowski SC, Carreira A |title=BRCA2 regulates DMC1-mediated recombination through the BRC repeats |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=113 |issue=13 |pages=3515–20 |year=2016 |pmid=26976601 |pmc=4822569 |doi=10.1073/pnas.1601691113 |bibcode=2016PNAS..113.3515M |doi-access=free }}</ref>  BRC repeats conform to a motif consisting of a sequence of about 35 highly conserved amino acids that are present at least once in all BRCA2-like proteins.  The BRCA2 BRC repeats stimulate joint molecule formation by promoting the interaction of single-stranded DNA (ssDNA) with DMC1.<ref name=Martinez />  The ssDNA complexed with DMC1 can pair with homologous ssDNA from another chromosome during the synopsis stage of [[meiosis]] to form a joint molecule, a central step in [[homologous recombination]]. Thus the BRC repeat sequences of BRCA2 appear to play a key role in recombinational repair of DNA damages during meiotic recombination.

Overall, it appears that homologous recombination during meiosis functions to repair DNA damages,{{Citation needed|date=December 2019|reason=removed citation to predatory publisher content}} and that BRCA2 plays a key role in performing this function.