title: Distinct Roles of Meiosis-Specific Cohesin Complexes in Mammalian Spermatogenesis.
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.
authors: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors: Uddipta
authors: U
authors: Biswas
authors: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors: Kai
authors: K
authors: Hempel
authors: Centro de Investigacion del Cancer (CSIC-USAL), Campus Miguel de Unamuno, Salamanca, Spain.
authors: Elena
authors: E
authors: Llano
authors: Centro de Investigacion del Cancer (CSIC-USAL), Campus Miguel de Unamuno, Salamanca, Spain.
authors: Alberto
authors: A
authors: Pendas
authors: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors: Rolf
authors: R
authors: Jessberger
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D002503:Centromere / Q000235:genetics; D002842:Chromatids / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D023902:Chromosome Pairing / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics; D004268:DNA-Binding Proteins; D008297:Male; D008322:Mammals; D008540:Meiosis / Q000235:genetics*; D049469:Meiotic Prophase I / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D013090:Spermatocytes / Q000254:growth & development; D013091:Spermatogenesis / Q000235:genetics*; D013573:Synaptonemal Complex / Q000235:genetics; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000097722:Cohesins; C556316:RAD21L protein, mouse; C465863:Rec8 protein, mouse; C438001:Smc1l2 protein, mouse; C489754:Sycp1 protein, mouse