Centromeric CENP-A loading requires accurate mitotic timing, which is linked to checkpoint proteins

AbstractA defining feature of centromeres is the presence of the histone H3 variant CENP-A that replaces H3 in a subset of centromeric nucleosomes. In Drosophila cultured cells CENP-A deposition at centromeres takes place during the metaphase stage of the cell cycle and strictly depends on the presence of its specific chaperone CAL1. How CENP-A loading is restricted to mitosis is unknown. We found that overexpression of CAL1 is associated with increased CENP-A levels at centromeres and completely uncouples CENP-A loading from mitosis. Moreover, CENP-A levels inversely correlate with mitosis duration. We found that CAL1 interacts with the spindle assembly checkpoint protein and RZZ complex component Zw10 and thus constitutes the anchor for the recruitment of RZZ. Therefore, CAL1 controls CENP-A incorporation at centromeres both quantitatively and temporally, connecting it to the spindle assembly checkpoint to ensure mitotic fidelity.

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Specific association of estrogen receptor beta with the cell cycle spindle assembly checkpoint protein, MAD2

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.050580997 ◽

2000 ◽

Vol 97 (6) ◽

pp. 2836-2839 ◽

Cited By ~ 45

Author(s):

G. Poelzl ◽

Y. Kasai ◽

N. Mochizuki ◽

P. W. Shaul ◽

M. Brown ◽

...

Keyword(s):

Cell Cycle ◽

Estrogen Receptor ◽

Spindle Assembly Checkpoint ◽

Estrogen Receptor Beta ◽

Spindle Assembly ◽

Checkpoint Protein ◽

Specific Association ◽

Receptor Beta ◽

Spindle Assembly Checkpoint Protein

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BubR1 is a spindle assembly checkpoint protein regulating meiotic cell cycle progression of mouse oocyte

Cell Cycle ◽

10.4161/cc.9.6.10957 ◽

2010 ◽

Vol 9 (6) ◽

pp. 1112-1121 ◽

Cited By ~ 64

Author(s):

Liang Wei ◽

Xing-Wei Liang ◽

Qing-Hua Zhang ◽

Mo Li ◽

Ju Yuan ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Spindle Assembly Checkpoint ◽

Spindle Assembly ◽

Mouse Oocyte ◽

Meiotic Cell ◽

Cycle Progression ◽

Checkpoint Protein ◽

Spindle Assembly Checkpoint Protein

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PRP4 is a spindle assembly checkpoint protein required for MPS1, MAD1, and MAD2 localization to the kinetochores

The Journal of Cell Biology ◽

10.1083/jcb.200703133 ◽

2007 ◽

Vol 179 (4) ◽

pp. 601-609 ◽

Cited By ~ 45

Author(s):

Emilie Montembault ◽

Stéphanie Dutertre ◽

Claude Prigent ◽

Régis Giet

Keyword(s):

Rna Processing ◽

Mitotic Spindle ◽

Messenger Rna ◽

Spindle Assembly Checkpoint ◽

Spindle Assembly ◽

Checkpoint Proteins ◽

Checkpoint Protein ◽

Anaphase Onset ◽

Spindle Microtubules ◽

Spindle Assembly Checkpoint Protein

The spindle checkpoint delays anaphase onset until every chromosome kinetochore has been efficiently captured by the mitotic spindle microtubules. In this study, we report that the human pre–messenger RNA processing 4 (PRP4) protein kinase associates with kinetochores during mitosis. PRP4 depletion by RNA interference induces mitotic acceleration. Moreover, we frequently observe lagging chromatids during anaphase leading to aneuploidy. PRP4-depleted cells do not arrest in mitosis after nocodazole treatment, indicating a spindle assembly checkpoint (SAC) failure. Thus, we find that PRP4 is necessary for recruitment or maintenance of the checkpoint proteins MPS1, MAD1, and MAD2 at the kinetochores. Our data clearly identify PRP4 as a previously unrecognized kinetochore component that is necessary to establish a functional SAC.

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Distinct responses to reduplicated chromosomes require distinct Mad2 responses

eLife ◽

10.7554/elife.15204 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 11

Author(s):

Benjamin M Stormo ◽

Donald T Fox

Keyword(s):

Cell Cycle ◽

Cancer Progression ◽

Sister Chromatid ◽

Spindle Assembly Checkpoint ◽

Polytene Chromosomes ◽

Spindle Assembly ◽

Tissue Development ◽

Checkpoint Protein ◽

Independent Mechanism ◽

Spindle Assembly Checkpoint Protein

Duplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromosome reduplication occurs in many contexts, including: polytene tissue development, polytene tumors, and following treatment with mitosis-blocking chemotherapeutics. However, mechanisms responding to or resolving polyteny during mitosis are poorly understood. Here, using Drosophila, we uncover two distinct reduplicated chromosome responses. First, when reduplicated polytene chromosomes persist into metaphase, an anaphase delay prevents tissue malformation and apoptosis. Second, reduplicated polytene chromosomes can also separate prior to metaphase through a spindle-independent mechanism termed Separation-Into-Recent-Sisters (SIRS). Both reduplication responses require the spindle assembly checkpoint protein Mad2. While Mad2 delays anaphase separation of metaphase polytene chromosomes, Mad2’s control of overall mitotic timing ensures efficient SIRS. Our results pinpoint mechanisms enabling continued proliferation after genome reduplication, a finding with implications for cancer progression and prevention.

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Distinct Responses to Reduplicated Chromosomes Require Distinct Mad2 Responses

10.1101/045781 ◽

2016 ◽

Author(s):

Benjamin M. Stormo ◽

Donald T. Fox

Keyword(s):

Cell Cycle ◽

Cancer Progression ◽

Sister Chromatid ◽

Spindle Assembly Checkpoint ◽

Polytene Chromosomes ◽

Spindle Assembly ◽

Tissue Development ◽

Checkpoint Protein ◽

Spindle Assembly Checkpoint Protein

ABSTRACTDuplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromosome reduplication occurs in many contexts, including: polytene tissue development, polytene tumors, and following treatment with mitosis-blocking chemotherapeutics. However, mechanisms responding to or resolving polyteny during mitosis are poorly understood. Here, using Drosophila, we uncover two distinct reduplicated chromosome responses. First, when reduplicated polytene chromosomes persist into metaphase, an anaphase delay prevents tissue malformation and apoptosis. Second, reduplicated polytene chromosomes can also separate prior to metaphase through a spindlePindependent mechanism termed Separation-Into-Recent-Sisters (SIRS). Both reduplication responses require the spindle assembly checkpoint protein Mad2. While Mad2 delays anaphase separation of metaphase polytene chromosomes, Mad2’s control of overall mitotic timing ensures efficient SIRS. Our results pinpoint mechanisms enabling continued proliferation after genome reduplication, a finding with implications for cancer progression and prevention.

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