Abstract
SummaryKinetochores assemble on chromosomes in mitosis to allow microtubules to attach and bring about accurate chromosome segregation. The kinases Cyclin B-Cdk1 and Aurora B are crucial for the formation of stable kinetochores. However, the activity of these two kinases appears to decline dramatically at centromeres during anaphase onset, precisely when microtubule attachments are required to move chromosomes toward opposite poles of the dividing cell. We find that, although Aurora B leaves centromeres at anaphase, a gradient of Aurora B activity centered on the central spindle is still able to phosphorylate kinetochore substrates such as Dsn1 to modulate kinetochore stability in anaphase and to regulate kinetochore disassembly as cells enter telophase. We provide a model to explain how Aurora B co-operates with Cyclin B-Cdk1 to maintain kinetochore function in anaphase.
Highlights
The mitotic spindle acts to segregate chromosomes accurately into daughters during cell division
In early mitosis, the kinase Aurora B plays a vital role in both kinetochore assembly and destabilizing incorrect kinetochore-microtubule attachments (Akiyoshi et al, 2013; Emanuele et al, 2008; Kim and Yu, 2015; Rago et al, 2015; Tanaka et al, 2002; Welburn et al, 2010; Yang et al, 2008), and Cyclin B-Cdk1 is required for key proteins to localize to the kinetochore (Gascoigne and Cheeseman, 2013; Gascoigne et al, 2011; Hara et al, 2018; Huis In ’t Veld et al, 2016; Nishino et al, 2013)
It is striking that key processes that control kinetochore assembly and function are driven by the activity of Cyclin B-Cdk1, which strongly declines at the metaphase-toanaphase transition (Clute and Pines, 1999; Murray et al, 1989), and Aurora B, which dissociates from centromeres and transfers to the central spindle in anaphase (Carmena et al, 2012)
Summary
The mitotic spindle acts to segregate chromosomes accurately into daughters during cell division. In early mitosis, the kinase Aurora B plays a vital role in both kinetochore assembly and destabilizing incorrect kinetochore-microtubule attachments (Akiyoshi et al, 2013; Emanuele et al, 2008; Kim and Yu, 2015; Rago et al, 2015; Tanaka et al, 2002; Welburn et al, 2010; Yang et al, 2008), and Cyclin B-Cdk is required for key proteins to localize to the kinetochore (Gascoigne and Cheeseman, 2013; Gascoigne et al, 2011; Hara et al, 2018; Huis In ’t Veld et al, 2016; Nishino et al, 2013) In many respects, these activities serve as a prelude to the most obvious function of kinetochores: driving chromosome movement to opposing spindle poles in anaphase, when kinetochore-spindle attachments are known to be stable (Asbury, 2017; Cimini et al, 2004; Zhai et al, 1995). A related and understudied question is how kinetochores are disassembled as cells enter telophase
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