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Robust Ordering of Anaphase Events by Adaptive Thresholds and Competing Degradation Pathways

Author:
Kamenz, Julia, Mihaljev, Tamara, Kubis, Armin, Legewie, Stefan, Hauf, Silke
Source:
Molecular cell 2015 v.60 pp. 446-459
ISSN:
1097-2765
Subject:
anaphase, chromosomes, cyclins, genome
Abstract:
The splitting of chromosomes in anaphase and their delivery into the daughter cells needs to be accurately executed to maintain genome stability. Chromosome splitting requires the degradation of securin, whereas the distribution of the chromosomes into the daughter cells requires the degradation of cyclin B. We show that cells encounter and tolerate variations in the abundance of securin or cyclin B. This makes the concurrent onset of securin and cyclin B degradation insufficient to guarantee that early anaphase events occur in the correct order. We uncover that the timing of chromosome splitting is not determined by reaching a fixed securin level, but that this level adapts to the securin degradation kinetics. In conjunction with securin and cyclin B competing for degradation during anaphase, this provides robustness to the temporal order of anaphase events. Our work reveals how parallel cell-cycle pathways can be temporally coordinated despite variability in protein concentrations.
Agid:
5540051