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Kinetochore

About: Kinetochore is a research topic. Over the lifetime, 5277 publications have been published within this topic receiving 347542 citations. The topic is also known as: GO:0000776 & Kinetochores.


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Journal ArticleDOI
TL;DR: Recent molecular analyses have begun to shed light on the complex interaction of the checkpoint proteins with kinetochores — structures that mediate the binding of spindle microtubules to chromosomes in mitosis.
Abstract: The spindle-assembly checkpoint is a safety device that monitors the attachment of spindle microtubules to kinetochores and ensures the fidelity of chromosome segregation in mitosis. Molecular studies are finally starting to reveal the mechanisms of checkpoint activation and inactivation.

2,197 citations

Journal ArticleDOI
03 Oct 1997-Cell
TL;DR: Three chromosmal proteins that prevent premature separation of sister chromatids in yeast are described, two of which are members of the SMC family, which are putative ATPases with coiled-coil domains.

1,545 citations

Journal ArticleDOI
09 Jul 2009-Nature
TL;DR: It is demonstrated that cells with multiple centrosomes rarely undergo multipolar cell divisions, and the progeny of these divisions are typically inviable, and it is proposed that this mechanism may be a common underlying cause of CIN in human cancer.
Abstract: Chromosomal instability (CIN) is a hallmark of many tumours and correlates with the presence of extra centrosomes. However, a direct mechanistic link between extra centrosomes and CIN has not been established. It has been proposed that extra centrosomes generate CIN by promoting multipolar anaphase, a highly abnormal division that produces three or more aneuploid daughter cells. Here we use long-term live-cell imaging to demonstrate that cells with multiple centrosomes rarely undergo multipolar cell divisions, and the progeny of these divisions are typically inviable. Thus, multipolar divisions cannot explain observed rates of CIN. In contrast, we observe that CIN cells with extra centrosomes routinely undergo bipolar cell divisions, but display a significantly increased frequency of lagging chromosomes during anaphase. To define the mechanism underlying this mitotic defect, we generated cells that differ only in their centrosome number. We demonstrate that extra centrosomes alone are sufficient to promote chromosome missegregation during bipolar cell division. These segregation errors are a consequence of cells passing through a transient 'multipolar spindle intermediate' in which merotelic kinetochore-microtubule attachment errors accumulate before centrosome clustering and anaphase. These findings provide a direct mechanistic link between extra centrosomes and CIN, two common characteristics of solid tumours. We propose that this mechanism may be a common underlying cause of CIN in human cancer.

1,313 citations

Journal ArticleDOI
TL;DR: The data suggest that Aurora B is required to generate unattached kinetochores on monooriented chromosomes, which in turn could promote bipolar attachment as well as maintain checkpoint signaling.
Abstract: The proper segregation of sister chromatids in mitosis depends on bipolar attachment of all chromosomes to the mitotic spindle. We have identified the small molecule Hesperadin as an inhibitor of chromosome alignment and segregation. Our data imply that Hesperadin causes this phenotype by inhibiting the function of the mitotic kinase Aurora B. Mammalian cells treated with Hesperadin enter anaphase in the presence of numerous monooriented chromosomes, many of which may have both sister kinetochores attached to one spindle pole (syntelic attachment). Hesperadin also causes cells arrested by taxol or monastrol to enter anaphase within <1 h, whereas cells in nocodazole stay arrested for 3–5 h. Together, our data suggest that Aurora B is required to generate unattached kinetochores on monooriented chromosomes, which in turn could promote bipolar attachment as well as maintain checkpoint signaling.

1,236 citations

Journal ArticleDOI
01 Jul 1999-Nature
TL;DR: It is shown that Esp1 causes the dissociation of Scc1 from chromosomes by stimulating its cleavage by proteolysis, and a mutant SCC1 is described that is resistant to Esp1-dependent cleavage and which blocks both sister-chromatid separation and the dissociations from chromosomes.
Abstract: Cohesion between sister chromatids is established during DNA replication and depends on a multiprotein complex called cohesin Attachment of sister kinetochores to the mitotic spindle during mitosis generates forces that would immediately split sister chromatids were it not opposed by cohesion Cohesion is essential for the alignment of chromosomes in metaphase but must be abolished for sister separation to start during anaphase In the budding yeast Saccharomyces cerevisiae, loss of sister-chromatid cohesion depends on a separating protein (separin) called Esp1 and is accompanied by dissociation from the chromosomes of the cohesion subunit Scc1 Here we show that Esp1 causes the dissociation of Scc1 from chromosomes by stimulating its cleavage by proteolysis A mutant Scc1 is described that is resistant to Esp1-dependent cleavage and which blocks both sister-chromatid separation and the dissociation of Scc1 from chromosomes The evolutionary conservation of separins indicates that the proteolytic cleavage of cohesion proteins might be a general mechanism for triggering anaphase

1,021 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023130
2022234
2021168
2020188
2019202
2018202