Abstract
We show that multiple, functionally specialized cohesin complexes mediate the establishment and two-step release of sister chromatid cohesion that underlies the production of haploid gametes. In C. elegans, the kleisin subunits REC-8 and COH-3/4 differ between meiotic cohesins and endow them with distinctive properties that specify how cohesins load onto chromosomes and then trigger and release cohesion. Unlike REC-8 cohesin, COH-3/4 cohesin becomes cohesive through a replication-independent mechanism initiated by the DNA double-stranded breaks that induce crossover recombination. Thus, break-induced cohesion also tethers replicated meiotic chromosomes. Later, recombination stimulates separase-independent removal of REC-8 and COH-3/4 cohesins from reciprocal chromosomal territories flanking the crossover site. This region-specific removal likely underlies the two-step separation of homologs and sisters. Unexpectedly, COH-3/4 performs cohesion-independent functions in synaptonemal complex assembly. This new model for cohesin function diverges from that established in yeast but likely applies directly to plants and mammals, which utilize similar meiotic kleisins.DOI: http://dx.doi.org/10.7554/eLife.03467.001
Highlights
In all organisms, faithful segregation of chromosomes during cell division is essential for genome stability
Levels of REC-8 and Structural Maintenance of Chromosomes (SMC)-3 were reduced in coh-4 coh-3 double mutants compared to wild-type animals, and both proteins appeared in dispersed puncta rather than in linear structures, as previously noted for the axial element HTP-3 (Severson et al, 2009)
These results provide strong evidence that REC-8 and COH-3/4 associate with chromosomes as subunits of independent meiotic cohesin complexes that differ in their kleisin subunit (Figure 1A)
Summary
Faithful segregation of chromosomes during cell division is essential for genome stability. 30% of human zygotes have abnormal chromosomal content at conception due to defects in meiosis Such aneuploidy is a leading cause of miscarriages and birth defects (Hassold and Hunt, 2001), and is thought to result, in part, from defects in sister chromatid cohesion (SCC) (Chiang et al, 2012; Jessberger, 2012; Nagaoka et al, 2012). SCC tethers replicated sister chromatids during mitosis and meiosis and is critical for accurate chromosome segregation. The mitotic kleisin Scc is replaced by the meiosis-specific kleisin Rec (Klein et al, 1999). This substitution is crucial for the reduction of ploidy
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