Distinct Roles of Meiosis-Specific Cohesin Complexes in Mammalian Spermatogenesis

PLoS Genet. 2016 Oct 28;12(10):e1006389. doi: 10.1371/journal.pgen.1006389. eCollection 2016 Oct.

Abstract

Mammalian meiocytes feature four meiosis-specific cohesin proteins in addition to ubiquitous ones, but the roles of the individual cohesin complexes are incompletely understood. To decipher the functions of the two meiosis-specific kleisins, REC8 or RAD21L, together with the only meiosis-specific SMC protein SMC1β, we generated Smc1β-/-Rec8-/- and Smc1β-/-Rad21L-/- mouse mutants. Analysis of spermatocyte chromosomes revealed that besides SMC1β complexes, SMC1α/RAD21 and to a small extent SMC1α/REC8 contribute to chromosome axis length. Removal of SMC1β and RAD21L almost completely abolishes all chromosome axes. The sex chromosomes do not pair in single or double mutants, and autosomal synapsis is impaired in all mutants. Super resolution microscopy revealed synapsis-associated SYCP1 aberrantly deposited between sister chromatids and on single chromatids in Smc1β-/-Rad21L-/- cells. All mutants show telomere length reduction and structural disruptions, while wild-type telomeres feature a circular TRF2 structure reminiscent of t-loops. There is no loss of centromeric cohesion in both double mutants at leptonema/early zygonema, indicating that, at least in the mutant backgrounds, an SMC1α/RAD21 complex provides centromeric cohesion at this early stage. Thus, in early prophase I the most prominent roles of the meiosis-specific cohesins are in axis-related features such as axis length, synapsis and telomere integrity rather than centromeric cohesion.

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics*
  • Centromere / genetics
  • Chromatids / genetics
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosome Pairing / genetics
  • Chromosome Segregation / genetics
  • DNA-Binding Proteins
  • Male
  • Mammals
  • Meiosis / genetics*
  • Meiotic Prophase I / genetics
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / genetics*
  • Phosphoproteins / genetics*
  • Spermatocytes / growth & development
  • Spermatogenesis / genetics*
  • Synaptonemal Complex / genetics

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • RAD21L protein, mouse
  • Rec8 protein, mouse
  • Smc1l2 protein, mouse
  • Sycp1 protein, mouse
  • cohesins

Grant support

This work was supported by grants fropm the Deutsche Forschungsgemeinschaft SPP1384 (RJ) and by the BFU (2014-59307-R) and JCyLe (AP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.