scholarly journals Condensin’s ATPase Machinery Drives and Dampens Mitotic Chromosome Condensation

2017 ◽  
Author(s):  
Ahmed M.O. Elbatsh ◽  
Jonne A. Raaijmakers ◽  
Robin H. van der Weide ◽  
Jelmi Kuit de Bos ◽  
Hans Teunissen ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Chromosome Condensation ◽  
The Other ◽  
Condensation Process ◽  
Total Absence ◽  
Sister Chromatids ◽  
Mitotic Chromosome Condensation ◽  
Do So

ABSTRACTChromosome condensation by condensin is essential for faithful chromosome segregation. Metazoans have two complexes, named condensin I and II. Both are thought to act by creating looped structures in DNA, but how they do so is unknown. Condensin’s SMC subunits together form a composite ATPase with two pseudo-symmetric ATPase sites. We reveal that these sites have opposite functions in the condensation process. One site drives condensation, while the other site rather has a dampening function. Mutation of this dampener site hyperactivates both condensin I and II complexes. We find that hyperactive condensin I efficiently shortens chromosomes in the total absence of condensin II. The two complexes form loops with different lengths, and specifically condensin II is key to the decatenation of sister chromatids and the formation of a straight chromosomal axis.

scholarly journals Mitotic chromosome condensation requires phosphorylation of the centromeric protein KNL-2 in C. elegans

2021 ◽  
Author(s):  
Joanna M Wenda ◽  
Reinier F Prosée ◽  
Caroline Gabus ◽  
Florian A Steiner
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Chromosome Condensation ◽  
Embryonic Lethality ◽  
Phosphorylation Sites ◽  
C Elegans ◽  
Microtubule Attachment ◽  
Centromeric Protein ◽  
Mitotic Chromosome Condensation

Centromeres are chromosomal regions that serve as sites for kinetochore formation and microtubule attachment, processes that are essential for chromosome segregation during mitosis. Centromeres are almost universally defined by the histone variant CENP-A. In the holocentric nematode C. elegans, CENP-A deposition depends on the loading factor KNL-2. Depletion of either CENP-A or KNL-2 results in defects in centromere maintenance, chromosome condensation and kinetochore formation, leading to chromosome segregation failure. Here, we show that KNL-2 is phosphorylated by CDK-1, and that mutation of three C-terminal phosphorylation sites causes chromosome segregation defects and an increase in embryonic lethality. In strains expressing phosphodeficient KNL-2, CENP-A and kinetochore proteins are properly localised, indicating that the role of KNL-2 in centromere maintenance is not affected. Instead, the mutant embryos exhibit reduced mitotic levels of condensin II on chromosomes and significant chromosome condensation impairment. Our findings separate the functions of KNL-2 in CENP-A loading and chromosome condensation and demonstrate that KNL-2 phosphorylation regulates the cooperation between centromeric regions and the condensation machinery in C. elegans.

scholarly journals Novel insights into mitotic chromosome condensation

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1807 ◽  
Author(s):  
Ewa Piskadlo ◽  
Raquel A. Oliveira
Keyword(s):  
Cell Division ◽  
Topoisomerase Ii ◽  
Mitotic Chromosome ◽  
Nuclear Division ◽  
Chromosome Condensation ◽  
Cell Division Cycle ◽  
Chromosome Organization ◽  
Condensation Process ◽  
Successful Completion ◽  
Mitotic Chromosome Condensation

The fidelity of mitosis is essential for life, and successful completion of this process relies on drastic changes in chromosome organization at the onset of nuclear division. The mechanisms that govern chromosome compaction at every cell division cycle are still far from full comprehension, yet recent studies provide novel insights into this problem, challenging classical views on mitotic chromosome assembly. Here, we briefly introduce various models for chromosome assembly and known factors involved in the condensation process (e.g. condensin complexes and topoisomerase II). We will then focus on a few selected studies that have recently brought novel insights into the mysterious way chromosomes are condensed during nuclear division.

scholarly journals Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis

2014 ◽  
Vol 205 (6) ◽  
pp. 781-790 ◽  
Author(s):  
Yuya Kagami ◽  
Keishi Nihira ◽  
Shota Wada ◽  
Masaya Ono ◽  
Mariko Honda ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Mitotic Chromosome ◽  
Early Stage ◽  
Chromosome Condensation ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Phosphorylation Event ◽  
G2 Phase ◽  
Mitotic Chromosome Condensation

During mitosis, genomic DNA is condensed into chromosomes to promote its equal segregation into daughter cells. Chromosome condensation occurs during cell cycle progression from G2 phase to mitosis. Failure of chromosome compaction at prophase leads to subsequent misregulation of chromosomes. However, the molecular mechanism that controls the early phase of mitotic chromosome condensation is largely unknown. Here, we show that Mps1 regulates initial chromosome condensation during mitosis. We identify condensin II as a novel Mps1-associated protein. Mps1 phosphorylates one of the condensin II subunits, CAP-H2, at Ser492 during mitosis, and this phosphorylation event is required for the proper loading of condensin II on chromatin. Depletion of Mps1 inhibits chromosomal targeting of condensin II and accurate chromosome condensation during prophase. These findings demonstrate that Mps1 governs chromosomal organization during the early stage of mitosis to facilitate proper chromosome segregation.

scholarly journals Topoisomerase IIα is essential for maintenance of mitotic chromosome structure

2020 ◽  
Vol 117 (22) ◽  
pp. 12131-12142 ◽  
Author(s):  
Christian F. Nielsen ◽  
Tao Zhang ◽  
Marin Barisic ◽  
Paul Kalitsis ◽  
Damien F. Hudson
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Chromosome Structure ◽  
Chromatin Condensation ◽  
Chromosome Condensation ◽  
Mitotic Chromosomes ◽  
Topoisomerase Iiα ◽  
Mitotic Chromosome Condensation

Topoisomerase IIα (TOP2A) is a core component of mitotic chromosomes and important for establishing mitotic chromosome condensation. The primary roles of TOP2A in mitosis have been difficult to decipher due to its multiple functions across the cell cycle. To more precisely understand the role of TOP2A in mitosis, we used the auxin-inducible degron (AID) system to rapidly degrade the protein at different stages of the human cell cycle. Removal of TOP2A prior to mitosis does not affect prophase timing or the initiation of chromosome condensation. Instead, it prevents chromatin condensation in prometaphase, extends the length of prometaphase, and ultimately causes cells to exit mitosis without chromosome segregation occurring. Surprisingly, we find that removal of TOP2A from cells arrested in prometaphase or metaphase cause dramatic loss of compacted mitotic chromosome structure and conclude that TOP2A is crucial for maintenance of mitotic chromosomes. Treatments with drugs used to poison/inhibit TOP2A function, such as etoposide and ICRF-193, do not phenocopy the effects on chromosome structure of TOP2A degradation by AID. Our data point to a role for TOP2A as a structural chromosome maintenance enzyme locking in condensation states once sufficient compaction is achieved.

scholarly journals Mitotic chromosome condensation requires phosphorylation of the centromeric protein KNL-2 in C. elegans

2021 ◽  
Author(s):  
Joanna M. Wenda ◽  
Reinier F. Prosée ◽  
Caroline Gabus ◽  
Florian A. Steiner
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Chromosome Condensation ◽  
Phosphorylation Sites ◽  
C Elegans ◽  
Microtubule Attachment ◽  
Centromeric Protein ◽  
Mitotic Chromosome Condensation

Centromeres are chromosomal regions that serve as sites for kinetochore formation and microtubule attachment, processes that are essential for chromosome segregation during mitosis. Centromeres are almost universally defined by the histone variant CENP-A. In the holocentric nematode C. elegans, CENP-A deposition depends on the loading factor KNL-2. Depletion of either CENP-A or KNL-2 results in defects in centromere maintenance, chromosome condensation and kinetochore formation, leading to chromosome segregation failure. Here, we show that KNL-2 is phosphorylated by CDK-1 in vitro, and that mutation of three C-terminal phosphorylation sites causes chromosome segregation defects and an increase in embryonic lethality. In strains expressing phosphodeficient KNL-2, CENP-A and kinetochore proteins are properly localised, indicating that the role of KNL-2 in centromere maintenance is not affected. Instead, the mutant embryos exhibit reduced mitotic levels of condensin II on chromosomes and significant chromosome condensation impairment. Our findings separate the functions of KNL-2 in CENP-A loading and chromosome condensation and demonstrate that KNL-2 phosphorylation regulates the cooperation between centromeric regions and the condensation machinery in C. elegans.

scholarly journals The dynamics of centromere motion through the metaphase-to-anaphase transition reveal a centromere separation order

2019 ◽  
Author(s):  
Jonathan W. Armond ◽  
Katie L. Dale ◽  
Nigel J. Burroughs ◽  
Andrew D. McAinsh ◽  
Elina Vladimirou
Keyword(s):  
Chromosome Segregation ◽  
High Speed ◽  
Daughter Cell ◽  
Mitotic Chromosome ◽  
Low Frequency ◽  
The Other ◽  
Bayesian Modelling ◽  
High Speed Imaging ◽  
Chromosome Dynamics ◽  
Sister Chromatids

AbstractDuring cell division, chromosomes align at the equator of the cell before sister chromatids separate to move to each daughter cell during anaphase. We use high-speed imaging, Bayesian modelling and quantitative analysis to examine the regulation of centromere dynamics through the metaphase-to-anaphase transition. We find that, contrary to the apparent instantaneous separation seen in low-frequency imaging, centromeres separate asynchronously over 1-2 minutes. The timing of separations negatively correlates with the centromere intersister distance during metaphase, which could potentially be explained by variable amounts of cohesion at centromeres. Depletion of condensin I increases this asynchrony. Depletion of condensin II, on the other hand, abolishes centromere metaphase oscillations and impairs centromere speed in anaphase. These results suggest that condensin complexes have broader direct roles in mitotic chromosome dynamics than previously believed and may be crucial for the regulation of chromosome segregation.

scholarly journals Chromosome Condensation Factor Brn1p Is Required for Chromatid Separation in Mitosis

2000 ◽  
Vol 11 (4) ◽  
pp. 1305-1313 ◽  
Author(s):  
Ilia I. Ouspenski ◽  
Olga A. Cabello ◽  
B. R. Brinkley
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Nuclear Protein ◽  
Chromosome Condensation ◽  
Temperature Sensitive ◽  
Condensin Complex ◽  
Chromatid Cohesion ◽  
Protein Functions ◽  
Mitotic Chromosome Condensation ◽  
Mutant Cells

This work describes BRN1, the budding yeast homologue of Drosophila Barren andXenopus condensin subunit XCAP-H. TheDrosophila protein is required for proper chromosome segregation in mitosis, and Xenopus protein functions in mitotic chromosome condensation. Mutant brn1 cells show a defect in mitotic chromosome condensation and sister chromatid separation and segregation in anaphase. Chromatid cohesion before anaphase is properly maintained in the mutants. Somebrn1 mutant cells apparently arrest in S-phase, pointing to a possible function for Brn1p at this stage of the cell cycle. Brn1p is a nuclear protein with a nonuniform distribution pattern, and its level is up-regulated at mitosis. Temperature-sensitive mutations ofBRN1 can be suppressed by overexpression of a novel geneYCG1, which is homologous to anotherXenopus condensin subunit, XCAP-G. Overexpression ofSMC2, a gene necessary for chromosome condensation, and a homologue of the XCAP-E condensin, does not suppress brn1, pointing to functional specialization of components of the condensin complex.

scholarly journals Integration of biological data by kernels on graph nodes allows prediction of new genes involved in mitotic chromosome condensation

2014 ◽  
Vol 25 (16) ◽  
pp. 2522-2536 ◽  
Author(s):  
Jean-Karim Hériché ◽  
Jon G. Lees ◽  
Ian Morilla ◽  
Thomas Walter ◽  
Boryana Petrova ◽  
...  
Keyword(s):  
Experimental Validation ◽  
Mitotic Chromosome ◽  
Chromosome Condensation ◽  
Biological Data ◽  
Cell Functions ◽  
Functional Relationships ◽  
New Genes ◽  
Public Data ◽  
Mitotic Chromosome Condensation ◽  
Graph Nodes

The advent of genome-wide RNA interference (RNAi)–based screens puts us in the position to identify genes for all functions human cells carry out. However, for many functions, assay complexity and cost make genome-scale knockdown experiments impossible. Methods to predict genes required for cell functions are therefore needed to focus RNAi screens from the whole genome on the most likely candidates. Although different bioinformatics tools for gene function prediction exist, they lack experimental validation and are therefore rarely used by experimentalists. To address this, we developed an effective computational gene selection strategy that represents public data about genes as graphs and then analyzes these graphs using kernels on graph nodes to predict functional relationships. To demonstrate its performance, we predicted human genes required for a poorly understood cellular function—mitotic chromosome condensation—and experimentally validated the top 100 candidates with a focused RNAi screen by automated microscopy. Quantitative analysis of the images demonstrated that the candidates were indeed strongly enriched in condensation genes, including the discovery of several new factors. By combining bioinformatics prediction with experimental validation, our study shows that kernels on graph nodes are powerful tools to integrate public biological data and predict genes involved in cellular functions of interest.

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