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WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation

Published in The journal of cell biology. 2021, vol. 220, no. 8, e202007171
Abstract Mutations in the WDR62 gene cause primary microcephaly, a pathological condition often associated with defective cell division that results in severe brain developmental defects. The precise function and localization of WDR62 within the mitotic spindle is, however, still under debate, as it has been proposed to act either at centrosomes or on the mitotic spindle. Here we explored the cellular functions of WDR62 in human epithelial cell lines using both short-term siRNA protein depletions and long-term CRISPR/Cas9 gene knockouts. We demonstrate that WDR62 localizes at spindle poles, promoting the recruitment of the microtubule-severing enzyme katanin. Depletion or loss of WDR62 stabilizes spindle microtubules due to insufficient microtubule minus-end depolymerization but does not affect plus-end microtubule dynamics. During chromosome segregation, WDR62 and katanin promote efficient poleward microtubule flux and favor the synchronicity of poleward movements in anaphase to prevent lagging chromosomes. We speculate that these lagging chromosomes might be linked to developmental defects in primary microcephaly.
PMID: 34137788
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Article (Published version) (6.3 MB) - public document Free access
Research group Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) (922)
Swiss National Science Foundation: 31003A_179413
(ISO format)
GUERREIRO, Amanda et al. WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation. In: The Journal of Cell Biology, 2021, vol. 220, n° 8, p. e202007171. doi: 10.1083/jcb.202007171 https://archive-ouverte.unige.ch/unige:154467

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Deposited on : 2021-09-06

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