Cohesin is required for meiotic spindle assembly independent of its role in cohesion in C. elegans

Accurate chromosome segregation requires a cohesin-mediated physical attachment between chromosomes that are to be segregated apart, and a bipolar spindle with microtubule plus ends emanating from exactly two poles toward the paired chromosomes. We asked whether the striking bipolar structure of C. elegans meiotic chromosomes is required for bipolarity of acentriolar female meiotic spindles by time-lapse imaging of mutants that lack cohesion between chromosomes. Both a spo-11 rec-8 coh-4 coh-3 quadruple mutant and a spo-11 rec-8 double mutant entered M phase with separated sister chromatids lacking any cohesion. However, the quadruple mutant formed an apolar spindle whereas the double mutant formed a bipolar spindle that segregated chromatids into two roughly equal masses. Residual non-cohesive COH-3/4-dependent cohesin on separated sister chromatids of the double mutant was sufficient to recruit haspin-dependent Aurora B kinase, which mediated bipolar spindle assembly in the apparent absence of chromosomal bipolarity. We hypothesized that cohesin-dependent Aurora B might activate or inhibit spindle assembly factors in a manner that would affect their localization on chromosomes and found that the chromosomal localization patterns of KLP-7 and CLS-2 correlated with Aurora B loading on chromosomes. These results demonstrate that cohesin is essential for spindle assembly and chromosome segregation independent of its role in sister chromatid cohesion. Author summary Meiosis is the process that reduces the number of chromosomes from four to one during the formation of eggs and sperm so that a fertilized egg has exactly two copies of each chromosome. Meiotic errors result in offspring with an incorrect number of chromosomes which results in prenatal death or birth defects. Accurate meiosis requires that the four chromosomes at the beginning of meiosis are attached to each other by a protein called cohesin and a structure called a spindle that pulls individual chromosomes in two directions. Here we show that in the roundworm, C. elegans, cohesin is required for building a spindle than can pull in two directions independently of its role in attaching chromosome copies to each other. Because cohesin is gradually lost in aging women, these results may clarify why aging women have an increasing incidence of babies with birth defects caused by an incorrect number of chromosomes.

Automated summary

Accurate chromosome segregation during meiosis requires both cohesion between chromosomes and the formation of a bipolar spindle. In this study, the researchers investigated whether the bipolar structure of C. elegans meiotic chromosomes is necessary for spindle polarity in the absence of cohesion. They found that while a mutant lacking cohesion formed an apolar spindle, a mutant with residual non-cohesive cohesin formed a bipolar spindle. The results suggest that cohesin is essential for spindle assembly and chromosome segregation independent of its role in sister chromatid cohesion.