Mammalian CNTD1 is critical for meiotic crossover maturation and deselection of excess precrossover sites

J Cell Biol. 2014 Jun 9;205(5):633-41. doi: 10.1083/jcb.201401122. Epub 2014 Jun 2.

Abstract

Meiotic crossovers (COs) are crucial for ensuring accurate homologous chromosome segregation during meiosis I. Because the double-strand breaks (DSBs) that initiate meiotic recombination greatly outnumber eventual COs, this process requires exquisite regulation to narrow down the pool of DSB intermediates that may form COs. In this paper, we identify a cyclin-related protein, CNTD1, as a critical mediator of this process. Disruption of Cntd1 results in failure to localize CO-specific factors MutLγ and HEI10 at designated CO sites and also leads to prolonged high levels of pre-CO intermediates marked by MutSγ and RNF212. These data show that maturation of COs is intimately coupled to deselection of excess pre-CO sites to yield a limited number of COs and that CNTD1 coordinates these processes by regulating the association between the RING finger proteins HEI10 and RNF212 and components of the CO machinery.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Cycle Proteins
  • Cell Differentiation
  • Chromosome Segregation
  • Chromosomes / ultrastructure
  • Crossing Over, Genetic*
  • Cyclins / genetics*
  • Cyclins / physiology*
  • DNA Breaks, Double-Stranded
  • Ligases / metabolism
  • Male
  • Meiosis*
  • Mice
  • Mice, Transgenic
  • Mutation
  • Phenotype
  • Recombination, Genetic
  • Sperm Count
  • Spermatocytes / cytology
  • Spermatocytes / metabolism
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • CNTD1 protein, mouse
  • Cell Cycle Proteins
  • Cyclins
  • Ccnb1ip1 protein, mouse
  • Ubiquitin-Protein Ligases
  • Ligases
  • Rnf212 protein, mouse