Antagonistic roles of ubiquitin ligase HEI10 and SUMO ligase RNF212 regulate meiotic recombination

Nat Genet. 2014 Feb;46(2):194-9. doi: 10.1038/ng.2858. Epub 2014 Jan 5.


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.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle Proteins
  • Crossing Over, Genetic / genetics*
  • Crossing Over, Genetic / physiology
  • Electrophoresis, Polyacrylamide Gel
  • In Situ Nick-End Labeling
  • Indoles
  • Ligases / antagonists & inhibitors*
  • Ligases / metabolism
  • Male
  • Meiosis / genetics*
  • Meiosis / physiology
  • Mice
  • Mice, Inbred C57BL
  • SUMO-1 Protein / metabolism
  • Spermatocytes / cytology
  • Spermatocytes / physiology
  • Statistics, Nonparametric
  • Synaptonemal Complex / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / antagonists & inhibitors*
  • Ubiquitin-Protein Ligases / metabolism


  • Cell Cycle Proteins
  • Indoles
  • SUMO-1 Protein
  • Ubiquitin
  • DAPI
  • Ccnb1ip1 protein, mouse
  • Ubiquitin-Protein Ligases
  • Ligases
  • Rnf212 protein, mouse