title: The logic and mechanism of homologous recombination partner choice.
abstract: Recombinational repair of spontaneous double-strand breaks (DSBs) exhibits sister bias. DSB-initiated meiotic recombination exhibits homolog bias. Physical analysis in yeast reveals that, in both cases, the recombination reaction intrinsically gives homolog bias. From this baseline default, cohesin intervenes to confer sister bias, likely independent of cohesion. In meiosis, cohesin's sister-biasing effect is counteracted by RecA homolog Rad51 and its mediators, plus meiotic RecA homolog Dmc1, which thereby restore intrinsic homolog bias. Meiotic axis complex Red1/Mek1/Hop1 participates by cleanly switching recombination from mitotic to meiotic mode, concomitantly activating Dmc1. We propose that a Rad51/DNA filament at one DSB end captures the intact sister, creating an anchor pad. This filament extends across the DSB site on the intact partner, precluding intersister strand exchange, thus forcing use of the homolog. Cohesin and Dmc1 interactively modulate this extension, with program-appropriate effects. In accord with this model, Rad51-mediated recombination in vivo requires the presence of a sister.
authors: Department of Life Sciences, Chung-Ang University, Seoul 156-756, Korea.
authors: Soogil
authors: S
authors: Hong
authors: Youngjin
authors: Y
authors: Sung
authors: Mi
authors: M
authors: Yu
authors: Minsu
authors: M
authors: Lee
authors: Nancy
authors: N
authors: Kleckner
authors: Keun P
authors: KP
authors: Kim
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D004271:DNA, Fungal / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination / Q000235:genetics*; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D008540:Meiosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D048369:MAP Kinase Kinase 1; D051135:Rad51 Recombinase; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C513033:DMC1 protein, S cerevisiae; C086672:HOP1 protein, S cerevisiae; C086673:RED1 protein, S cerevisiae; C495151:RAD51 protein, S cerevisiae
references: Genetics. 1992 Oct;132(2):387-402
references: 1427035
references: Cell. 1997 Sep 19;90(6):1123-35
references: 9323140
references: Genes Dev. 2007 Jul 15;21(14):1758-66
references: 17639081
references: Cell. 2010 Dec 10;143(6):924-37
references: 21145459
references: Cell. 1994 Jan 14;76(1):51-63
references: 8287479
references: PLoS Genet. 2011 Jul;7(7):e1002148
references: 21779174
references: Mol Microbiol. 2009 Jul;73(1):89-102
references: 19496932
references: PLoS Biol. 2010 Oct 19;8(10):e1000520
references: 20976044
references: Nucleic Acids Res. 2012 Jul;40(13):5795-818
references: 22467216
references: Genetics. 2003 Dec;165(4):1831-42
references: 14704169
references: Genetics. 1998 Sep;150(1):173-88
references: 9725837
references: Cell. 2001 Jul 13;106(1):59-70
references: 11461702
references: J Biol Chem. 2012 Aug 17;287(34):28727-37
references: 22761450
references: Nature. 2010 Apr 8;464(7290):937-41
references: 20348905
references: J Biol Chem. 2012 Jun 8;287(24):20231-9
references: 22465956
references: Cell. 2005 Sep 23;122(6):861-73
references: 16179256
references: Cell. 2001 Jul 13;106(1):47-57
references: 11461701
references: Biochem Soc Trans. 2001 May;29(Pt 2):196-201
references: 11356153
references: Mol Biol Cell. 2004 Jan;15(1):11-23
references: 14595109
references: Mol Biol Cell. 2007 Oct;18(10):4062-73
references: 17671161
references: Genes Dev. 2006 Jul 1;20(13):1766-75
references: 16818607
references: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10814-9
references: 11005857
references: Science. 2012 Sep 7;337(6099):1222-5
references: 22955832
references: PLoS Genet. 2010 May 13;6(5):e1000948
references: 20485519
references: PLoS Genet. 2013;9(12):e1003978
references: 24367271
references: Nat Commun. 2013;4:1676
references: 23575680
references: Genes Cells. 1997 Aug;2(8):487-98
references: 9348039
references: Genetics. 2005 Mar;169(3):1275-89
references: 15654096
references: PLoS Genet. 2010 Jul 01;6(7):e1001006
references: 20617204
references: Cell. 2010 Apr 2;141(1):94-106
references: 20371348
references: Genes Dev. 2006 Jul 1;20(13):1685-91
references: 16818601
references: Mol Biol Cell. 2009 Feb;20(3):1030-47
references: 19073884
references: J Cell Biol. 2005 Oct 24;171(2):241-53
references: 16230461
references: J Biol Chem. 2012 Jan 6;287(2):1566-75
references: 22115747
references: Cell. 2007 Jul 27;130(2):259-72
references: 17662941
references: Plant Cell. 2012 May;24(5):2058-70
references: 22589466