title: The dual role of HOP2 in mammalian meiotic homologous recombination.
abstract: Deletion of Hop2 in mice eliminates homologous chromosome synapsis and disrupts double-strand break (DSB) repair through homologous recombination. HOP2 in vitro shows two distinctive activities: when it is incorporated into a HOP2-MND1 complex it stimulates DMC1 and RAD51 recombination activities and the purified HOP2 alone is proficient in promoting strand invasion. We observed that a fraction of Mnd1(-/-) spermatocytes, which express HOP2 but apparently have inactive DMC1 and RAD51 due to lack of the HOP2-MND1 complex, exhibits a high level of chromosome synapsis and that most DSBs in these spermatocytes are repaired. This suggests that DSB repair catalyzed solely by HOP2 supports homologous chromosome pairing and synapsis. In addition, we show that in vitro HOP2 promotes the co-aggregation of ssDNA with duplex DNA, binds to ssDNA leading to unstacking of the bases, and promotes the formation of a three-strand synaptic intermediate. However, HOP2 shows distinctive mechanistic signatures as a recombinase. Namely, HOP2-mediated strand exchange does not require ATP and, in contrast to DMC1, joint molecules formed by HOP2 are more sensitive to mismatches and are efficiently dissociated by RAD54. We propose that HOP2 may act as a recombinase with specific functions in meiosis.
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, 73104 OK, USA, Department of Cell Biology, Oklahoma University Health Science Center, Oklahoma City, 73126 OK, USA, Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892 MD, USA, Institute of Molecular Genetics of the Russian Academy of Sciences, 123182 Moscow, Russia, Biomedical Research Center, National Institute of Aging, Baltimore, 21224 MA, USA and Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, 19102 PA, USA.
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Pezza
authors.forename: Oleg N
authors.initials: ON
authors.lastname: Voloshin
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Volodin
authors.forename: Kingsley A
authors.initials: KA
authors.lastname: Boateng
authors.forename: Marina A
authors.initials: MA
authors.lastname: Bellani
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Mazin
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Camerini-Otero
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D023902:Chromosome Pairing; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000378:metabolism; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D028044:Phosphate-Binding Proteins; D045522:Recombinases / Q000378:metabolism*; D059767:Recombinational DNA Repair
chemical_list: D018797:Cell Cycle Proteins; C513032:Dmc1 protein, mouse; C501202:Hop2 protein, mouse; C501203:Mnd1 protein, mouse; D009687:Nuclear Proteins; D028044:Phosphate-Binding Proteins; D045522:Recombinases; D004265:DNA Helicases; C552322:rad54b protein, mouse