Sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1.

<h4>Background</h4>Microtubule-targeting drugs induce mitotic delay at pro-metaphase by preventing the spindle assembly checkpoint to be satisfied. However, especially after prolonged treatments, cells can escape this arrest in a process called mitotic slippage. The mechanisms underlying...

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Autores principales:	Ana Lúcia Mena, Eric W-F Lam, Sukalyan Chatterjee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6cbeb95a029543c4ba9004c19b55beb2
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spelling	oai:doaj.org-article:6cbeb95a029543c4ba9004c19b55beb22021-11-18T07:03:53ZSustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1.1932-620310.1371/journal.pone.0013037https://doaj.org/article/6cbeb95a029543c4ba9004c19b55beb22010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20927403/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Microtubule-targeting drugs induce mitotic delay at pro-metaphase by preventing the spindle assembly checkpoint to be satisfied. However, especially after prolonged treatments, cells can escape this arrest in a process called mitotic slippage. The mechanisms underlying the spindle assembly checkpoint and slippage are not fully understood. It has been generally accepted that during mitosis there is a temporary shutdown of high-energy-consuming processes, such as transcription and translation. However, the synthesis of specific proteins is maintained or up-regulated since protein synthesis is necessary for entry into and progression through mitosis.<h4>Methodology/principal findings</h4>In this work we investigated whether the mitotic arrest caused by the mitotic checkpoint is independent of transcription and translation. By using immunofluorescent microscopy and western blotting, we demonstrate that inhibition of either of these processes induces a shortening of the mitotic arrest caused by the nocodazole treatment, and ultimately leads to mitotic slippage. Our western blotting and RTQ-PCR results show that inhibition of transcription during mitotic arrest does not affect the expression of the spindle checkpoint proteins, whereas it induces a significant decrease in the mRNA and protein levels of Cyclin B1. The exogenous expression of Cyclin B1 substantially rescued the mitotic phenotype in nocodazole cells treated with the inhibitors of transcription and translation.<h4>Conclusions/significance</h4>This work emphasizes the importance of transcription and translation for the maintenance of the spindle assembly checkpoint, suggesting the existence of a mechanism dependent on cyclin B1 gene regulation during mitosis. We propose that continuous transcription of mitotic regulators is required to sustain the activation of the spindle assembly checkpoint.Ana Lúcia MenaEric W-F LamSukalyan ChatterjeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana Lúcia Mena Eric W-F Lam Sukalyan Chatterjee Sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1.
description	<h4>Background</h4>Microtubule-targeting drugs induce mitotic delay at pro-metaphase by preventing the spindle assembly checkpoint to be satisfied. However, especially after prolonged treatments, cells can escape this arrest in a process called mitotic slippage. The mechanisms underlying the spindle assembly checkpoint and slippage are not fully understood. It has been generally accepted that during mitosis there is a temporary shutdown of high-energy-consuming processes, such as transcription and translation. However, the synthesis of specific proteins is maintained or up-regulated since protein synthesis is necessary for entry into and progression through mitosis.<h4>Methodology/principal findings</h4>In this work we investigated whether the mitotic arrest caused by the mitotic checkpoint is independent of transcription and translation. By using immunofluorescent microscopy and western blotting, we demonstrate that inhibition of either of these processes induces a shortening of the mitotic arrest caused by the nocodazole treatment, and ultimately leads to mitotic slippage. Our western blotting and RTQ-PCR results show that inhibition of transcription during mitotic arrest does not affect the expression of the spindle checkpoint proteins, whereas it induces a significant decrease in the mRNA and protein levels of Cyclin B1. The exogenous expression of Cyclin B1 substantially rescued the mitotic phenotype in nocodazole cells treated with the inhibitors of transcription and translation.<h4>Conclusions/significance</h4>This work emphasizes the importance of transcription and translation for the maintenance of the spindle assembly checkpoint, suggesting the existence of a mechanism dependent on cyclin B1 gene regulation during mitosis. We propose that continuous transcription of mitotic regulators is required to sustain the activation of the spindle assembly checkpoint.
format	article
author	Ana Lúcia Mena Eric W-F Lam Sukalyan Chatterjee
author_facet	Ana Lúcia Mena Eric W-F Lam Sukalyan Chatterjee
author_sort	Ana Lúcia Mena
title	Sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1.
title_short	Sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1.
title_full	Sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1.
title_fullStr	Sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1.
title_full_unstemmed	Sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1.
title_sort	sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin b1.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/6cbeb95a029543c4ba9004c19b55beb2
work_keys_str_mv	AT analuciamena sustainedspindleassemblycheckpointresponserequiresdenovotranscriptionandtranslationofcyclinb1 AT ericwflam sustainedspindleassemblycheckpointresponserequiresdenovotranscriptionandtranslationofcyclinb1 AT sukalyanchatterjee sustainedspindleassemblycheckpointresponserequiresdenovotranscriptionandtranslationofcyclinb1
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Sustained spindle-assembly checkpoint response requires de novo transcription and translation of cyclin B1.

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