Apr 1, 2020

Deubiquitylase UCHL3 drives error correction at kinetochores and chromosome segregation independent of spindle assembly checkpoint

BioRxiv : the Preprint Server for Biology
Fabian ZimmerIzabela Sumara

Abstract

Equal segregation of chromosomes during mitosis ensures euploidy of daughter cells. Defects in this process may result in imbalance in chromosomal composition and cellular transformation. Two surveillance pathways, the spindle assembly checkpoint (SAC) and the error-correction (EC), exist at kinetochores that monitor microtubule attachment and faithful segregation of chromosomes at the metaphase to anaphase transition. However, the molecular understanding of the interplay between EC and SAC signaling remains limited. Here we describe a role of deubiquitylase UCHL3 in the regulation of EC pathway during mitosis. Downregulation or inhibition of UCHL3 leads to improper attachments of chromosomes to spindle microtubules and to chromosome alignment defects during metaphase. Frequent segregation errors during anaphase and consequently aneuploidy is also observed upon inactivation of UCHL3. Surprisingly, UCHL3 is not involved in SAC signaling as both recruitment of SAC proteins to kinetochores and timely anaphase onset are not perturbed in UCHL3-deficient cells. Mechanistically, UCHL3 interacts with and deubiquitylates the mitotic kinase Aurora B known to drive both SAC and EC signaling. UCHL3 promotes interaction of Aurora B with MCA...Continue Reading

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