Meiosis-specific cohesin mediates homolog recognition in mouse spermatocytes

Genes Dev. 2014 Mar 15;28(6):594-607. doi: 10.1101/gad.237313.113. Epub 2014 Mar 3.

Abstract

During meiosis, homologous chromosome (homolog) pairing is promoted by several layers of regulation that include dynamic chromosome movement and meiotic recombination. However, the way in which homologs recognize each other remains a fundamental issue in chromosome biology. Here, we show that homolog recognition or association initiates upon entry into meiotic prophase before axis assembly and double-strand break (DSB) formation. This homolog association develops into tight pairing only during or after axis formation. Intriguingly, the ability to recognize homologs is retained in Sun1 knockout spermatocytes, in which telomere-directed chromosome movement is abolished, and this is the case even in Spo11 knockout spermatocytes, in which DSB-dependent DNA homology search is absent. Disruption of meiosis-specific cohesin RAD21L precludes the initial association of homologs as well as the subsequent pairing in spermatocytes. These findings suggest the intriguing possibility that homolog recognition is achieved primarily by searching for homology in the chromosome architecture as defined by meiosis-specific cohesin rather than in the DNA sequence itself.

Keywords: DSB; bouquet; cohesin; homolog pairing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Pairing / genetics
  • Chromosome Pairing / physiology*
  • Chromosomes / metabolism
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism
  • Female
  • Gene Knockout Techniques
  • In Situ Hybridization, Fluorescence
  • Male
  • Meiosis / genetics
  • Meiosis / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Spermatocytes / metabolism
  • Spermatocytes / physiology*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Microtubule-Associated Proteins
  • RAD21L protein, mouse
  • SUN1 protein, mouse
  • cohesins
  • Endodeoxyribonucleases
  • meiotic recombination protein SPO11