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McNally, K. P.

Publications and source records attributed to McNally, K. P..

2 recordsLinked to original sources

Mechanisms of Meiotic Spindle Initiation in Caenorhabditis elegans Oocytes

In many animal species, the oocyte meiotic spindle, which is required for chromosome segregation, forms without centrosomes. In some systems, Ran-GEF on chromatin initiates spindle assembly. We found that in C. elegans oocytes, endogenously-tagged Ran-GEF dissociates from chromatin during spindle assembly but re-associates during meiotic anaphase. Meiotic spindle assembly occurred after auxin-induced degradation of Ran-GEF but anaphase I was faster than controls and extrusion of the first polar body frequently failed. In search of a possible alternative pathway for spindle assembly, we found that soluble tubulin concentrates in the nuclear volume during germinal vesicle breakdown. We found that the concentration of soluble tubulin in the metaphase spindle region is enclosed by ER sheets which exclude cytoplasmic organelles including mitochondria and yolk granules. Measurement of the volume occupied by yolk granules and mitochondria indicated that volume exclusion would be sufficient to explain the concentration of tubulin in the spindle volume. We suggest that this concentration of soluble tubulin may be a redundant mechanism promoting spindle assembly near chromosomes.

cell biology↗

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 analyzing mutants that lack cohesion between chromosomes. Both a spo-11, rec-8, coh-3, coh-4 quadruple mutant and a spo-11, rec-8 double mutant entered M phase with single 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 single chromatids of the double mutant was sufficient to recruit haspin- dependent Aurora B kinase, which regulated the localization of the spindle-assembly factors CLASP-2 and kinesin-13 to mediate bipolar spindle assembly in the apparent absence of chromosomal bipolarity. These results demonstrate that cohesin is essential for spindle assembly and chromosome segregation independent of its role in sister chromatid cohesion.

cell biology↗