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.
Highlights
After completing premeiotic DNA replication mammalian germ cells enter meiosis and undergo two meiotic cell divisions without any further DNA replication
Meiosis features specific chromosome structures and dynamics, and we revealed individual contributions of meiotic cohesin complexes to chromosome axes length, centromeric cohesion, telomere integrity and synapsis
Analysis of testis sections from adult Smc1β-/-Rec8-/- and Smc1β-/-Rad21L-/- mice was performed by staining with DAPI, an antibody specific for SYCP3 (“anti SYCP3”), which is a component of the axial element (AE) and lateral elements (LEs), and either anti γH2AX or anti SYCP1 (Fig 2A–2D)
Summary
After completing premeiotic DNA replication mammalian germ cells enter meiosis and undergo two meiotic cell divisions without any further DNA replication. The compacted AEs start to pair in zygonema, i.e. the two homologous pairs (homologs) of sister chromatids synapse and form the synaptonemal complex (SC), which is complete in pachynema. Each pair of sister chromatids is held together by cohesins, the two pairs are embedded in SC proteins. Homologous recombination between the two homologs requires the introduction of programmed double strand breaks (DSBs) by the topoisomerase-type enzyme SPO11. These breaks, which can be visualized by staining for double-strand break repair proteins such as the meiosis-specific DMC1, are introduced in leptonema and are processed into recombination intermediates until pachynema. In diplonema the SC between homologs disassembles, the homologs desynapse, but remain linked through a few chiasmata, the sites of meiotic recombination, until the homologs are separated in anaphase of meiosis I and the recombination process is completed
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