Coordination of Chromosome Alignment and Mitotic Progression Chromosome-Based Ran Signal

Hoi Y. Li; Win Pin Ng; Wong Chi Hang; Pablo A. Iglesias; Yixian Zheng

doi:10.4161/cc.6.15.4487

Aurora at the pole and equator: overlapping functions of Aurora kinases in the mitotic spindle

Open Biology ◽

10.1098/rsob.120185 ◽

2013 ◽

Vol 3 (3) ◽

pp. 120185 ◽

Cited By ~ 65

Author(s):

Helfrid Hochegger ◽

Nadia Hégarat ◽

Jose B. Pereira-Leal

Keyword(s):

Chromosome Segregation ◽

Mitotic Spindle ◽

Aurora Kinase ◽

Spindle Pole ◽

Aurora A ◽

Mitotic Progression ◽

Aurora Kinases ◽

Mitotic Kinases ◽

Chromosome Alignment ◽

Spindle Microtubules

The correct assembly and timely disassembly of the mitotic spindle is crucial for the propagation of the genome during cell division. Aurora kinases play a central role in orchestrating bipolar spindle establishment, chromosome alignment and segregation. In most eukaryotes, ranging from amoebas to humans, Aurora activity appears to be required both at the spindle pole and the kinetochore, and these activities are often split between two different Aurora paralogues, termed Aurora A and B. Polar and equatorial functions of Aurora kinases have generally been considered separately, with Aurora A being mostly involved in centrosome dynamics, whereas Aurora B coordinates kinetochore attachment and cytokinesis. However, double inactivation of both Aurora A and B results in a dramatic synergy that abolishes chromosome segregation. This suggests that these two activities jointly coordinate mitotic progression. Accordingly, recent evidence suggests that Aurora A and B work together in both spindle assembly in metaphase and disassembly in anaphase. Here, we provide an outlook on these shared functions of the Auroras, discuss the evolution of this family of mitotic kinases and speculate why Aurora kinase activity may be required at both ends of the spindle microtubules.

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Cyclin-dependent kinase 1-mediated AMPK phosphorylation regulates chromosome alignment and mitotic progression

Journal of Cell Science ◽

10.1242/jcs.236000 ◽

2019 ◽

Vol 132 (20) ◽

pp. jcs236000 ◽

Cited By ~ 3

Author(s):

Seth Stauffer ◽

Yongji Zeng ◽

Montserrat Santos ◽

Jiuli Zhou ◽

Yuanhong Chen ◽

...

Keyword(s):

Cyclin Dependent Kinase ◽

Mitotic Progression ◽

Ampk Phosphorylation ◽

Chromosome Alignment

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Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1508791112 ◽

2015 ◽

Vol 112 (33) ◽

pp. E4546-E4555 ◽

Cited By ~ 36

Author(s):

Zhen Dou ◽

Xing Liu ◽

Wenwen Wang ◽

Tongge Zhu ◽

Xinghui Wang ◽

...

Keyword(s):

Spindle Assembly Checkpoint ◽

Tetratricopeptide Repeat ◽

Mitotic Progression ◽

Microtubule Attachment ◽

Spatiotemporal Regulation ◽

Monopolar Spindle ◽

Evolutionarily Conserved ◽

Repeat Domain ◽

Chromosome Alignment ◽

Tetratricopeptide Repeat Domain

The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C–MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.

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Leaving no-one behind: how CENP-E facilitates chromosome alignment

Essays in Biochemistry ◽

10.1042/ebc20190073 ◽

2020 ◽

Vol 64 (2) ◽

pp. 313-324 ◽

Cited By ~ 3

Author(s):

Benjamin Craske ◽

Julie P.I. Welburn

Keyword(s):

Motor Activity ◽

Recent Work ◽

Transport Mechanism ◽

Genomic Stability ◽

Mitotic Progression ◽

Kinesin Motor ◽

Independent Manner ◽

Chromosome Congression ◽

Chromosome Alignment ◽

Microtubule Motor

Abstract Chromosome alignment and biorientation is essential for mitotic progression and genomic stability. Most chromosomes align at the spindle equator in a motor-independent manner. However, a subset of polar kinetochores fail to bi-orient and require a microtubule motor-based transport mechanism to move to the cell equator. Centromere Protein E (CENP-E/KIF10) is a kinesin motor from the Kinesin-7 family, which localizes to unattached kinetochores during mitosis and utilizes plus-end directed microtubule motility to slide mono-oriented chromosomes to the spindle equator. Recent work has revealed how CENP-E cooperates with chromokinesins and dynein to mediate chromosome congression and highlighted its role at aligned chromosomes. Additionally, we have gained new mechanistic insights into the targeting and regulation of CENP-E motor activity at the kinetochore. Here, we will review the function of CENP-E in chromosome congression, the pathways that contribute to CENP-E loading at the kinetochore, and how CENP-E activity is regulated during mitosis.

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