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What is the role of WDR62 in mitosis?

Defense Thèse de doctorat : Univ. Genève, 2021 - Sc. Vie 99 - 2021/03/24
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. To explore the cellular functions of this protein in human epithelial cell lines, I used both short-term siRNA protein depletions and long-term CRISPR/Cas9 gene knockouts. Results indicated that WDR62 localizes to microtubule minus-ends and is essential to localize the microtubule-severing enzyme katanin at spindle poles. 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 synchronous poleward movements in anaphase to prevent lagging chromosomes that might be linked to developmental defects in primary microcephaly.
Keywords Mitotic spindleMicrotubule minus-endChromosome segregation
URN: urn:nbn:ch:unige-1515518
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Research group Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) (922)
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GUERREIRO, Amanda. What is the role of WDR62 in mitosis?. Université de Genève. Thèse, 2021. doi: 10.13097/archive-ouverte/unige:151551 https://archive-ouverte.unige.ch/unige:151551

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Deposited on : 2021-05-10

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