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Nat Genet. 2013 Mar;45(3):269-78. doi: 10.1038/ng.2541. Epub 2013 Feb 10.

RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis.

Author information

1
Howard Hughes Medical Institute, University of California, Davis, Davis, California, USA.

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.

PMID:
23396135
PMCID:
PMC4245152
DOI:
10.1038/ng.2541
[Indexed for MEDLINE]
Free PMC Article

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