Abstract
During mitosis, the interaction of kinetochores (KTs) with microtubules (MTs) drives chromosome congression to the spindle equator and supports the segregation of sister chromatids. Faithful genome partition critically relies on the ability of chromosomes to establish and maintain proper amphitelic end-on attachments, a configuration in which sister KTs are connected to robust MT fibers emanating from opposite spindle poles. Because the capture of spindle MTs by KTs is error prone, cells use mechanisms that sense and correct inaccurate KT-MT interactions before committing to segregate sister chromatids in anaphase. If left unresolved, these errors can result in the unequal distribution of chromosomes and lead to aneuploidy, a hallmark of cancer. In this review, we provide an overview of the molecular strategies that monitor the formation and fine-tuning of KT-MT attachments. We describe the complex network of proteins that operates at the KT-MT interface and discuss how AURORA B and PLK1 coordinate several concurrent events so that the stability of KT-MT attachments is precisely modulated throughout mitotic progression. We also outline updated knowledge on how the RZZ complex is regulated to ensure the formation of end-on attachments and the fidelity of mitosis.
Highlights
The distribution of a full complement of chromosomes to each daughter cell at the end of mitosis represents a decisive step for the maintenance of genomic stability
We focus on the regulatory functions of PLK1 and AURORA B towards KT-MT attachment stability and address how these functions are timely controlled during mitosis
The ability to bind to the MT surface is probably dictated by the intact CH domain of NDC80. Both mutant complexes could not track with depolymerizing MT ends when placed under force to mimic load and detached from the MT tip (Huis In ’t Veld et al, 2019). These results suggest that the N-terminal tail in NDC80 is required for force-coupling to dynamic MTs and that AURORA B modulates this interaction
Summary
Received: 30 September 2021 Accepted: 13 January 2022 Published: 28 January 2022. Citation: Barbosa J, Sunkel CE and Conde C (2022) The Role of Mitotic Kinases and the RZZ Complex in KinetochoreMicrotubule Attachments: Doing the. The interaction of kinetochores (KTs) with microtubules (MTs) drives chromosome congression to the spindle equator and supports the segregation of sister chromatids. Because the capture of spindle MTs by KTs is error prone, cells use mechanisms that sense and correct inaccurate KT-MT interactions before committing to segregate sister chromatids in anaphase. If left unresolved, these errors can result in the unequal distribution of chromosomes and lead to aneuploidy, a hallmark of cancer. We outline updated knowledge on how the RZZ complex is regulated to ensure the formation of end-on attachments and the fidelity of mitosis
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