Dynamic Architecture of DNA Repair Complexes and the Synaptonemal Complex at Sites of Meiotic Recombination

Cell. 2018 Jun 14;173(7):1678-1691.e16. doi: 10.1016/j.cell.2018.03.066. Epub 2018 May 10.

Abstract

Meiotic double-strand breaks (DSBs) are generated and repaired in a highly regulated manner to ensure formation of crossovers (COs) while also enabling efficient non-CO repair to restore genome integrity. We use structured-illumination microscopy to investigate the dynamic architecture of DSB repair complexes at meiotic recombination sites in relationship to the synaptonemal complex (SC). DSBs resected at both ends are converted into inter-homolog repair intermediates harboring two populations of BLM helicase and RPA, flanking a single population of MutSγ. These intermediates accumulate until late pachytene, when repair proteins disappear from non-CO sites and CO-designated sites become enveloped by SC-central region proteins, acquire a second MutSγ population, and lose RPA. These and other data suggest that the SC may protect CO intermediates from being dismantled inappropriately and promote CO maturation by generating a transient CO-specific repair compartment, thereby enabling differential timing and outcome of repair at CO and non-CO sites.

Keywords: DNA repair; meiosis; recombination; super-resolution; synaptonemal complex.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA Breaks, Double-Stranded
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • Imaging, Three-Dimensional
  • Meiosis*
  • Microscopy
  • Prophase
  • Rad51 Recombinase / metabolism
  • Recombination, Genetic / genetics*
  • Replication Protein A / metabolism
  • Synaptonemal Complex / chemistry
  • Synaptonemal Complex / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • MSH-5 protein, C elegans
  • Replication Protein A
  • Rad51 Recombinase