Abstract
During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastrophe.
Highlights
Reproducing organisms reduce their genomic content by half in the gametes such that the normal chromosome copy number is restored in the zygote
As homologous chromosomes engage in recombination, matching DNA strands between broken and intact template chromosomes become intertwined in repair intermediates called Joint Molecules
We show that a highly conserved protein complex called the Structural Maintenance of Chromosomes 5/6 (Smc5/6) complex is important for regulating the choice of recombination template as well as for the resolution of Joint Molecules that is required for chromosomes to separate
Summary
Reproducing organisms reduce their genomic content by half in the gametes such that the normal chromosome copy number is restored in the zygote. Homologous chromosomes (homologs) have to pair and segregate to opposite spindle poles at the first division of meiosis. Homolog pairing and segregation depends upon the developmental induction of hundreds of double-strand breaks (DSBs) throughout the genome (150–300 DSBs in yeasts and mammals) [1]. A subset of DSB repair events lead to crossover formation. These reciprocal exchanges between homologs combine with sister-chromatid cohesion to form chiasmata, the physical connections that aid bi-orientation of homologs on the meiosis I spindle. Centromere cohesion is protected to allow biorientation and accurate segregation of sister chromatids on the meiosis-II spindles [3,4,5]
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