HTP-3 links DSB formation with homolog pairing and crossing over during C. elegans meiosis

Dev Cell. 2008 Feb;14(2):263-74. doi: 10.1016/j.devcel.2007.11.016.

Abstract

Repair of the programmed meiotic double-strand breaks (DSBs) that initiate recombination must be coordinated with homolog pairing to generate crossovers capable of directing chromosome segregation. Chromosome pairing and synapsis proceed independently of recombination in worms and flies, suggesting a paradoxical lack of coregulation. Here, we find that the meiotic axis component HTP-3 links DSB formation with homolog pairing and synapsis. HTP-3 forms complexes with the DSB repair components MRE-11/RAD-50 and the meiosis-specific axis component HIM-3. Loss of htp-3 or mre-11 recapitulates meiotic phenotypes consistent with a failure to generate DSBs, suggesting that HTP-3 associates with MRE-11/RAD-50 in a complex required for meiotic DSB formation. Loss of HTP-3 eliminates HIM-3 localization to axes and HIM-3-dependent homolog alignment, synapsis, and crossing over. Our study reveals a mechanism for coupling meiotic DSB formation with homolog pairing through the essential participation of an axis component with complexes mediating both processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Chromatin / metabolism
  • Chromosome Pairing*
  • Chromosome Positioning
  • Crossing Over, Genetic*
  • DNA Breaks, Double-Stranded*
  • DNA Repair
  • Meiosis*
  • Mutation / genetics
  • Protein Binding
  • Protein Transport
  • RNA Interference

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Chromatin
  • HTP-3 protein, C elegans