Crossover assurance and crossover interference are distinctly regulated by the ZMM proteins during yeast meiosis

Nat Genet. 2008 Mar;40(3):299-309. doi: 10.1038/ng.83. Epub 2008 Feb 24.


Meiotic crossing-over is highly regulated such that each homolog pair typically receives at least one crossover (assurance) and adjacent crossovers are widely spaced (interference). Here we provide evidence that interference and assurance are mechanistically distinct processes that are separated by mutations in a new ZMM (Zip, Msh, Mer) protein from Saccharomyces cerevisiae, Spo16. Like other zmm mutants, spo16 cells have defects in both crossing-over and synaptonemal complex formation. Unlike in previously characterized zmm mutants, the residual crossovers in spo16 cells show interference comparable to that in the wild type. Spo16 interacts with a second ZMM protein, Spo22 (also known as Zip4), and spo22 mutants also show normal interference. Notably, assembly of the MutS homologs Msh4 and Msh5 on chromosomes occurs in both spo16 and spo22, but not in other zmm mutants. We suggest that crossover interference requires the normal assembly of recombination complexes containing Msh4 and Msh5 but does not require Spo16- and Spo22-dependent extension of synaptonemal complexes. In contrast, crossover assurance requires all ZMM proteins and full-length synaptonemal complexes.

Publication types

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

MeSH terms

  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Pairing / genetics
  • Chromosome Pairing / physiology*
  • Chromosomes, Fungal
  • Crossing Over, Genetic / physiology*
  • DNA-Binding Proteins / physiology
  • Dimerization
  • In Situ Hybridization, Fluorescence
  • Meiosis / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / physiology*
  • Models, Biological
  • Mutant Proteins / physiology
  • Nuclear Proteins
  • Organisms, Genetically Modified
  • Protein Binding
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Synaptonemal Complex / genetics
  • Synaptonemal Complex / physiology
  • Tissue Distribution
  • Ubiquitin-Protein Ligases / physiology


  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MSH4 protein, S cerevisiae
  • Microtubule-Associated Proteins
  • Mutant Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Spo16 protein, S cerevisiae
  • Spo22 protein, S cerevisiae
  • Zip1 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • Zip3 protein, S cerevisiae