Distinct Roles of Meiosis-Specific Cohesin Complexes in Mammalian Spermatogenesis

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 SMC1 beta, we generated Smc1 beta(-/-) Rec8(-/-) and Smc1 beta(-/-) Rad21L(-/-) mouse mutants. Analysis of spermatocyte chromosomes revealed that besides SMC1 beta complexes, SMC1 alpha/RAD21 and to a small extent SMC1 alpha/REC8 contribute to chromosome axis length. Removal of SMC1 beta 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 Smc1 beta(-/-) 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 SMC1 alpha/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.