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ATR and a Chk1-Aurora B pathway coordinate postmitotic genome surveillance with cytokinetic abscission

Aurora B regulates cytokinesis timing and plays a central role in the abscission checkpoint. Cellular events monitored by this checkpoint are beginning to be elucidated, yet signaling pathways upstream of Aurora B in this context remain poorly understood. Here we reveal a new connection between post...

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Detalles Bibliográficos
Autores principales: Mackay, Douglas R., Ullman, Katharine S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462940/
https://www.ncbi.nlm.nih.gov/pubmed/25904336
http://dx.doi.org/10.1091/mbc.E14-11-1563
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author Mackay, Douglas R.
Ullman, Katharine S.
author_facet Mackay, Douglas R.
Ullman, Katharine S.
author_sort Mackay, Douglas R.
collection PubMed
description Aurora B regulates cytokinesis timing and plays a central role in the abscission checkpoint. Cellular events monitored by this checkpoint are beginning to be elucidated, yet signaling pathways upstream of Aurora B in this context remain poorly understood. Here we reveal a new connection between postmitotic genome surveillance and cytokinetic abscission. Underreplicated DNA lesions are known to be transmitted through mitosis and protected in newly formed nuclei by recruitment of 53BP1 and other proteins until repair takes place. We find that this genome surveillance initiates before completion of cytokinesis. Elevating replication stress increases this postmitotic process and delays cytokinetic abscission by keeping the abscission checkpoint active. We further find that ATR activity in midbody-stage cells links postmitotic genome surveillance to abscission timing and that Chk1 integrates this and other signals upstream of Aurora B to regulate when the final step in the physical separation of daughter cells occurs.
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spelling pubmed-44629402015-08-30 ATR and a Chk1-Aurora B pathway coordinate postmitotic genome surveillance with cytokinetic abscission Mackay, Douglas R. Ullman, Katharine S. Mol Biol Cell Articles Aurora B regulates cytokinesis timing and plays a central role in the abscission checkpoint. Cellular events monitored by this checkpoint are beginning to be elucidated, yet signaling pathways upstream of Aurora B in this context remain poorly understood. Here we reveal a new connection between postmitotic genome surveillance and cytokinetic abscission. Underreplicated DNA lesions are known to be transmitted through mitosis and protected in newly formed nuclei by recruitment of 53BP1 and other proteins until repair takes place. We find that this genome surveillance initiates before completion of cytokinesis. Elevating replication stress increases this postmitotic process and delays cytokinetic abscission by keeping the abscission checkpoint active. We further find that ATR activity in midbody-stage cells links postmitotic genome surveillance to abscission timing and that Chk1 integrates this and other signals upstream of Aurora B to regulate when the final step in the physical separation of daughter cells occurs. The American Society for Cell Biology 2015-06-15 /pmc/articles/PMC4462940/ /pubmed/25904336 http://dx.doi.org/10.1091/mbc.E14-11-1563 Text en © 2015 Mackay and Ullman. 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). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Mackay, Douglas R.
Ullman, Katharine S.
ATR and a Chk1-Aurora B pathway coordinate postmitotic genome surveillance with cytokinetic abscission
title ATR and a Chk1-Aurora B pathway coordinate postmitotic genome surveillance with cytokinetic abscission
title_full ATR and a Chk1-Aurora B pathway coordinate postmitotic genome surveillance with cytokinetic abscission
title_fullStr ATR and a Chk1-Aurora B pathway coordinate postmitotic genome surveillance with cytokinetic abscission
title_full_unstemmed ATR and a Chk1-Aurora B pathway coordinate postmitotic genome surveillance with cytokinetic abscission
title_short ATR and a Chk1-Aurora B pathway coordinate postmitotic genome surveillance with cytokinetic abscission
title_sort atr and a chk1-aurora b pathway coordinate postmitotic genome surveillance with cytokinetic abscission
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462940/
https://www.ncbi.nlm.nih.gov/pubmed/25904336
http://dx.doi.org/10.1091/mbc.E14-11-1563
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