title: RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis.
abstract: Crossing-over ensures accurate chromosome segregation during meiosis, and every pair of chromosomes obtains at least one crossover, even though the majority of recombination sites yield non-crossovers. A putative regulator of crossing-over is RNF212, which is associated with variation in crossover rates in humans. We show that mouse RNF212 is essential for crossing-over, functioning to couple chromosome synapsis to the formation of crossover-specific recombination complexes. Selective localization of RNF212 to a subset of recombination sites is shown to be a key early step in the crossover designation process. RNF212 acts at these sites to stabilize meiosis-specific recombination factors, including the MutSγ complex (MSH4-MSH5). We infer that selective stabilization of key recombination proteins is a fundamental feature of meiotic crossover control. Haploinsufficiency indicates that RNF212 is a limiting factor for crossover control and raises the possibility that human alleles may alter the amount or stability of RNF212 and be risk factors for aneuploid conditions.
authors: Howard Hughes Medical Institute, University of California, Davis, Davis, California, USA.
authors: April
authors: A
authors: Reynolds
authors: Huanyu
authors: H
authors: Qiao
authors: Ye
authors: Y
authors: Yang
authors: Jefferson K
authors: JK
authors: Chen
authors: Neil
authors: N
authors: Jackson
authors: Kajal
authors: K
authors: Biswas
authors: J Kim
authors: JK
authors: Holloway
authors: Frédéric
authors: F
authors: Baudat
authors: Bernard
authors: B
authors: de Massy
authors: Jeremy
authors: J
authors: Wang
authors: Christer
authors: C
authors: Höög
authors: Paula E
authors: PE
authors: Cohen
authors: Neil
authors: N
authors: Hunter
mesh_terms: D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics; D003434:Crossing Over, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D006801:Humans; D008025:Ligases; D008540:Meiosis; D051379:Mice; D011995:Recombination, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C502328:Msh4 protein, mouse; C512847:Msh5 protein, mouse; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C527435:RNF212 protein, human
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