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The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events

Here we have used siRNAs and time-lapse epifluorescence microscopy to examine the roles of various candidate mitotic cyclins in chromatin condensation in HeLa cells. Knocking down cyclin A2 resulted in a substantial (∼7 h) delay in chromatin condensation and histone H3 phosphorylation, and expressin...

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Detalles Bibliográficos
Autores principales: Gong, Delquin, Ferrell, James E.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938381/
https://www.ncbi.nlm.nih.gov/pubmed/20660152
http://dx.doi.org/10.1091/mbc.E10-05-0393
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author Gong, Delquin
Ferrell, James E.
author_facet Gong, Delquin
Ferrell, James E.
author_sort Gong, Delquin
collection PubMed
description Here we have used siRNAs and time-lapse epifluorescence microscopy to examine the roles of various candidate mitotic cyclins in chromatin condensation in HeLa cells. Knocking down cyclin A2 resulted in a substantial (∼7 h) delay in chromatin condensation and histone H3 phosphorylation, and expressing an siRNA-resistant form of cyclin A2 partially rescued chromatin condensation. There was no detectable delay in DNA replication in the cyclin A2 knockdowns, arguing that the delay in chromatin condensation is not secondary to a delay in S-phase completion. Cyclin A2 is required for the activation and nuclear accumulation of cyclin B1-Cdk1, raising the possibility that cyclin B1-Cdk1 mediates the effects of cyclin A2. Consistent with this possibility, we found that chromatin condensation was tightly associated temporally with the redistribution of cyclin B1 to the nucleus. Moreover, a constitutively nuclear cyclin B1 rescued chromatin condensation in cyclin A2 knockdown cells. On the other hand, knocking down cyclin B1 delayed chromatin condensation by only about one hour. Our working hypothesis is that active, nuclear cyclin B1-Cdk1 normally cooperates with cyclin A2 to bring about early mitotic events. Because cyclin A2 is present only during the early stages of mitosis, we asked whether cyclin B knockdown might have more dramatic defects on late mitotic events. Consistent with this possibility, we found that cyclin B1- and cyclin B1/B2-knockdown cells had difficulty in maintaining a mitotic arrest in the presence of nocodazole. Taken together, these data suggest that cyclin A2 helps initiate mitosis, in part through its effects on cyclin B1, and that cyclins B1 and B2 are particularly critical for the maintenance of the mitotic state.
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spelling pubmed-29383812010-11-30 The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events Gong, Delquin Ferrell, James E. Mol Biol Cell Articles Here we have used siRNAs and time-lapse epifluorescence microscopy to examine the roles of various candidate mitotic cyclins in chromatin condensation in HeLa cells. Knocking down cyclin A2 resulted in a substantial (∼7 h) delay in chromatin condensation and histone H3 phosphorylation, and expressing an siRNA-resistant form of cyclin A2 partially rescued chromatin condensation. There was no detectable delay in DNA replication in the cyclin A2 knockdowns, arguing that the delay in chromatin condensation is not secondary to a delay in S-phase completion. Cyclin A2 is required for the activation and nuclear accumulation of cyclin B1-Cdk1, raising the possibility that cyclin B1-Cdk1 mediates the effects of cyclin A2. Consistent with this possibility, we found that chromatin condensation was tightly associated temporally with the redistribution of cyclin B1 to the nucleus. Moreover, a constitutively nuclear cyclin B1 rescued chromatin condensation in cyclin A2 knockdown cells. On the other hand, knocking down cyclin B1 delayed chromatin condensation by only about one hour. Our working hypothesis is that active, nuclear cyclin B1-Cdk1 normally cooperates with cyclin A2 to bring about early mitotic events. Because cyclin A2 is present only during the early stages of mitosis, we asked whether cyclin B knockdown might have more dramatic defects on late mitotic events. Consistent with this possibility, we found that cyclin B1- and cyclin B1/B2-knockdown cells had difficulty in maintaining a mitotic arrest in the presence of nocodazole. Taken together, these data suggest that cyclin A2 helps initiate mitosis, in part through its effects on cyclin B1, and that cyclins B1 and B2 are particularly critical for the maintenance of the mitotic state. The American Society for Cell Biology 2010-09-15 /pmc/articles/PMC2938381/ /pubmed/20660152 http://dx.doi.org/10.1091/mbc.E10-05-0393 Text en © 2010 by The American Society for Cell Biology This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
spellingShingle Articles
Gong, Delquin
Ferrell, James E.
The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events
title The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events
title_full The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events
title_fullStr The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events
title_full_unstemmed The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events
title_short The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events
title_sort roles of cyclin a2, b1, and b2 in early and late mitotic events
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938381/
https://www.ncbi.nlm.nih.gov/pubmed/20660152
http://dx.doi.org/10.1091/mbc.E10-05-0393
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