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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromosome Segregation / genetics
  • Crossing Over, Genetic*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dosage Compensation, Genetic
  • Humans
  • Ligases
  • Meiosis*
  • Mice
  • Recombination, Genetic*
  • Ubiquitin-Protein Ligases / genetics*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Msh4 protein, mouse
  • Msh5 protein, mouse
  • Ubiquitin-Protein Ligases
  • Ligases
  • RNF212 protein, human