title: Antagonistic roles of ubiquitin ligase HEI10 and SUMO ligase RNF212 regulate meiotic recombination.
abstract: Crossover recombination facilitates the accurate segregation of homologous chromosomes during meiosis. In mammals, poorly characterized regulatory processes ensure that every pair of chromosomes obtains at least one crossover, even though most recombination sites yield non-crossovers. Designation of crossovers involves selective localization of the SUMO ligase RNF212 to a minority of recombination sites, where it stabilizes pertinent factors such as MutSγ (ref. 4). Here we show that the ubiquitin ligase HEI10 (also called CCNB1IP1) is essential for this crossover/non-crossover differentiation process. In HEI10-deficient mice, RNF212 localizes to most recombination sites, and dissociation of both RNF212 and MutSγ from chromosomes is blocked. Consequently, recombination is impeded, and crossing over fails. In wild-type mice, HEI10 accumulates at designated crossover sites, suggesting that it also has a late role in implementing crossing over. As with RNF212, dosage sensitivity for HEI10 indicates that it is a limiting factor for crossing over. We suggest that SUMO and ubiquitin have antagonistic roles during meiotic recombination that are balanced to effect differential stabilization of recombination factors at crossover and non-crossover sites.
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, Davis, Davis, California, USA. [2] Department of Microbiology & Molecular Genetics, University of California, Davis, Davis, California, USA.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Qiao
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, Davis, Davis, California, USA. [2] Department of Microbiology & Molecular Genetics, University of California, Davis, Davis, California, USA.
authors.forename: H B D
authors.initials: HB
authors.lastname: Prasada Rao
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, Davis, Davis, California, USA. [2] Department of Microbiology & Molecular Genetics, University of California, Davis, Davis, California, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, Davis, Davis, California, USA. [2] Department of Microbiology & Molecular Genetics, University of California, Davis, Davis, California, USA.
authors.forename: Jared H
authors.initials: JH
authors.lastname: Fong
authors.affiliation: Department of Biology, Middlebury College, Middlebury, Vermont, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Cloutier
authors.affiliation: Department of Biology, Middlebury College, Middlebury, Vermont, USA.
authors.forename: Dekker C
authors.identifier: 0000000241605730
authors.initials: DC
authors.lastname: Deacon
authors.affiliation: Department of Biology, Middlebury College, Middlebury, Vermont, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Nagel
authors.affiliation: Department of Biology, Middlebury College, Middlebury, Vermont, USA.
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Swartz
authors.affiliation: Department of Molecular Biology & Genetics, Cornell University College of Veterinary Medicine, Ithaca, New York, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Strong
authors.affiliation: Center for Reproductive Genomics, Department of Biomedical Sciences, Cornell University, Ithaca, New York, USA.
authors.forename: J Kim
authors.initials: JK
authors.lastname: Holloway
authors.affiliation: Center for Reproductive Genomics, Department of Biomedical Sciences, Cornell University, Ithaca, New York, USA.
authors.forename: Paula E
authors.initials: PE
authors.lastname: Cohen
authors.affiliation: Department of Molecular Biology & Genetics, Cornell University College of Veterinary Medicine, Ithaca, New York, USA.
authors.forename: John
authors.initials: J
authors.lastname: Schimenti
authors.affiliation: Department of Biology, Middlebury College, Middlebury, Vermont, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ward
authors.affiliation: 1] Howard Hughes Medical Institute, University of California, Davis, Davis, California, USA. [2] Department of Microbiology & Molecular Genetics, University of California, Davis, Davis, California, USA. [3] Department of Molecular & Cellular Biology, University of California, Davis, Davis, California, USA. [4] Department of Cell Biology & Human Anatomy, University of California, Davis, Davis, California, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Hunter
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D003434:Crossing Over, Genetic / Q000235:genetics* / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D020287:In Situ Nick-End Labeling; D007211:Indoles; D008025:Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D025842:SUMO-1 Protein / Q000378:metabolism; D013090:Spermatocytes / Q000166:cytology / Q000502:physiology; D018709:Statistics, Nonparametric; D013573:Synaptonemal Complex / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D007211:Indoles; D025842:SUMO-1 Protein; D025801:Ubiquitin; C007293:DAPI; C523697:Ccnb1ip1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C581307:Rnf212 protein, mouse