title: A dominant, recombination-defective allele of Dmc1 causing male-specific sterility.
abstract: DMC1 is a meiosis-specific homolog of bacterial RecA and eukaryotic RAD51 that can catalyze homologous DNA strand invasion and D-loop formation in vitro. DMC1-deficient mice and yeast are sterile due to defective meiotic recombination and chromosome synapsis. The authors identified a male dominant sterile allele of Dmc1, Dmc1(Mei11), encoding a missense mutation in the L2 DNA binding domain that abolishes strand invasion activity. Meiosis in male heterozygotes arrests in pachynema, characterized by incomplete chromosome synapsis and no crossing-over. Young heterozygous females have normal litter sizes despite having a decreased oocyte pool, a high incidence of meiosis I abnormalities, and susceptibility to premature ovarian failure. Dmc1(Mei11) exposes a sex difference in recombination in that a significant portion of female oocytes can compensate for DMC1 deficiency to undergo crossing-over and complete gametogenesis. Importantly, these data demonstrate that dominant alleles of meiosis genes can arise and propagate in populations, causing infertility and other reproductive consequences due to meiotic prophase I defects.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Bannister
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Pezza
authors.forename: Janet R
authors.initials: JR
authors.lastname: Donaldson
authors.forename: Dirk G
authors.initials: DG
authors.lastname: de Rooij
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Schimenti
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Camerini-Otero
authors.forename: John C
authors.initials: JC
authors.lastname: Schimenti
mesh_terms: D000483:Alleles; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D007247:Infertility, Female / Q000473:pathology; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D009865:Oocytes / Q000166:cytology; D010053:Ovary / Q000473:pathology; D028044:Phosphate-Binding Proteins; D011995:Recombination, Genetic / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C513032:Dmc1 protein, mouse; D009687:Nuclear Proteins; D028044:Phosphate-Binding Proteins