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.

Meiotic cycle checkpoints in mammalian oocytes

Zygote ◽  
1994 ◽  
Vol 2 (4) ◽  
pp. 351-354 ◽  
Author(s):  
Josef Fulka ◽  
Judy Bradshaw ◽  
Robert Moor
Keyword(s):  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Mitotic Cell ◽  
Mitotic Cell Cycle ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Chromosomal Segregation ◽  
Nuclear Events ◽  
Last Stage ◽  
Meiotic Cycle

Recent Spectacular achievements have enabled the identification of key molecules responsible for mitotic cell cycle progression through the stages of G1, the gap before DNA replication; S, the phase of DNA synthesis; G2, the gap before chromosome segregation; and M, mitosis itself. The last stage has been most intensively studied, where MPE, maturation promotion factor, has been found responsible for the nuclear events associated with chromosomal segregation and the prodcution of two identical daughter cells (see Murray & Hunt, 1993).

Epigenetic dynamics across the cell cycle

2010 ◽  
Vol 48 ◽  
pp. 107-120 ◽  
Author(s):  
Tony Bou Kheir ◽  
Anders H. Lund
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Chromatin Condensation ◽  
Chromatin Modifications ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Mammalian Cell Cycle ◽  
Regulate Cell Cycle Progression

Progression of the mammalian cell cycle depends on correct timing and co-ordination of a series of events, which are managed by the cellular transcriptional machinery and epigenetic mechanisms governing genome accessibility. Epigenetic chromatin modifications are dynamic across the cell cycle, and are shown to influence and be influenced by cell-cycle progression. Chromatin modifiers regulate cell-cycle progression locally by controlling the expression of individual genes and globally by controlling chromatin condensation and chromosome segregation. The cell cycle, on the other hand, ensures a correct inheritance of epigenetic chromatin modifications to daughter cells. In this chapter, we summarize the current knowledge on the dynamics of epigenetic chromatin modifications during progression of the cell cycle.

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 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 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 A Human Condensin Complex Containing hCAP-C–hCAP-E and CNAP1, a Homolog of Xenopus XCAP-D2, Colocalizes with Phosphorylated Histone H3 during the Early Stage of Mitotic Chromosome Condensation

2000 ◽  
Vol 20 (18) ◽  
pp. 6996-7006 ◽  
Author(s):  
John A. Schmiesing ◽  
Heather C. Gregson ◽  
Sharleen Zhou ◽  
Kyoko Yokomori
Keyword(s):  
Mammalian Cells ◽  
Structural Changes ◽  
Mitotic Chromosome ◽  
Early Stage ◽  
Histone H3 ◽  
Chromosome Condensation ◽  
Early Prophase ◽  
Mitotic Chromosomes ◽  
Condensin Complex ◽  
Mitotic Chromosome Condensation

ABSTRACT Structural maintenance of chromosomes (SMC) family proteins play critical roles in structural changes of chromosomes. Previously, we identified two human SMC family proteins, hCAP-C and hCAP-E, which form a heterodimeric complex (hCAP-C–hCAP-E) in the cell. Based on the sequence conservation and mitotic chromosome localization, hCAP-C–hCAP-E was determined to be the human ortholog of theXenopus SMC complex, XCAP-C–XCAP-E. XCAP-C–XCAP-E is a component of the multiprotein complex termed condensin, required for mitotic chromosome condensation in vitro. However, presence of such a complex has not been demonstrated in mammalian cells. Coimmunoprecipitation of the endogenous hCAP-C–hCAP-E complex from HeLa extracts identified a 155-kDa protein interacting with hCAP-C–hCAP-E, termed condensation-related SMC-associated protein 1 (CNAP1). CNAP1 associates with mitotic chromosomes and is homologous toXenopus condensin component XCAP-D2, indicating the presence of a condensin complex in human cells. Chromosome association of human condensin is mitosis specific, and the majority of condensin dissociates from chromosomes and is sequestered in the cytoplasm throughout interphase. However, a subpopulation of the complex was found to remain on chromosomes as foci in the interphase nucleus. During late G2/early prophase, the larger nuclear condensin foci colocalize with phosphorylated histone H3 clusters on partially condensed regions of chromosomes. These results suggest that mitosis-specific function of human condensin may be regulated by cell cycle-specific subcellular localization of the complex, and the nuclear condensin that associates with interphase chromosomes is involved in the reinitiation of mitotic chromosome condensation in conjunction with phosphorylation of histone H3.

scholarly journals Recent Progress on the Localization of the Spindle Assembly Checkpoint Machinery to Kinetochores

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 278 ◽  
Author(s):  
Zhen Dou ◽  
Diogjena Prifti ◽  
Ping Gui ◽  
Xing Liu ◽  
Sabine Elowe ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Genome Stability ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Progression ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Microtubule Attachment ◽  
Surveillance Mechanism

Faithful chromosome segregation during mitosis is crucial for maintaining genome stability. The spindle assembly checkpoint (SAC) is a surveillance mechanism that ensures accurate mitotic progression. Defective SAC signaling leads to premature sister chromatid separation and aneuploid daughter cells. Mechanistically, the SAC couples the kinetochore microtubule attachment status to the cell cycle progression machinery. In the presence of abnormal kinetochore microtubule attachments, the SAC prevents the metaphase-to-anaphase transition through a complex kinase-phosphatase signaling cascade which results in the correct balance of SAC components recruited to the kinetochore. The correct kinetochore localization of SAC proteins is a prerequisite for robust SAC signaling and, hence, accurate chromosome segregation. Here, we review recent progresses on the kinetochore recruitment of core SAC factors.

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.

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