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Residual Cdk1/2 activity after DNA damage promotes senescence
In response to DNA damage, a cell can be forced to permanently exit the cell cycle and become senescent. Senescence provides an early barrier against tumor development by preventing proliferation of cells with damaged DNA. By studying single cells, we show that Cdk activity persists after DNA damage...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418196/ https://www.ncbi.nlm.nih.gov/pubmed/28345297 http://dx.doi.org/10.1111/acel.12588 |
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author | Müllers, Erik Silva Cascales, Helena Burdova, Kamila Macurek, Libor Lindqvist, Arne |
author_facet | Müllers, Erik Silva Cascales, Helena Burdova, Kamila Macurek, Libor Lindqvist, Arne |
author_sort | Müllers, Erik |
collection | PubMed |
description | In response to DNA damage, a cell can be forced to permanently exit the cell cycle and become senescent. Senescence provides an early barrier against tumor development by preventing proliferation of cells with damaged DNA. By studying single cells, we show that Cdk activity persists after DNA damage until terminal cell cycle exit. This low level of Cdk activity not only allows cell cycle progression, but also promotes cell cycle exit at a decision point in G2 phase. We find that residual Cdk1/2 activity is required for efficient p21 production, allowing for nuclear sequestration of Cyclin B1, subsequent APC/C(C) (dh1)‐dependent degradation of mitotic inducers and induction of senescence. We suggest that the same activity that triggers mitosis in an unperturbed cell cycle enforces senescence in the presence of DNA damage, ensuring a robust response when most needed. |
format | Online Article Text |
id | pubmed-5418196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54181962017-06-01 Residual Cdk1/2 activity after DNA damage promotes senescence Müllers, Erik Silva Cascales, Helena Burdova, Kamila Macurek, Libor Lindqvist, Arne Aging Cell Original Articles In response to DNA damage, a cell can be forced to permanently exit the cell cycle and become senescent. Senescence provides an early barrier against tumor development by preventing proliferation of cells with damaged DNA. By studying single cells, we show that Cdk activity persists after DNA damage until terminal cell cycle exit. This low level of Cdk activity not only allows cell cycle progression, but also promotes cell cycle exit at a decision point in G2 phase. We find that residual Cdk1/2 activity is required for efficient p21 production, allowing for nuclear sequestration of Cyclin B1, subsequent APC/C(C) (dh1)‐dependent degradation of mitotic inducers and induction of senescence. We suggest that the same activity that triggers mitosis in an unperturbed cell cycle enforces senescence in the presence of DNA damage, ensuring a robust response when most needed. John Wiley and Sons Inc. 2017-03-26 2017-06 /pmc/articles/PMC5418196/ /pubmed/28345297 http://dx.doi.org/10.1111/acel.12588 Text en © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Müllers, Erik Silva Cascales, Helena Burdova, Kamila Macurek, Libor Lindqvist, Arne Residual Cdk1/2 activity after DNA damage promotes senescence |
title | Residual Cdk1/2 activity after DNA damage promotes senescence |
title_full | Residual Cdk1/2 activity after DNA damage promotes senescence |
title_fullStr | Residual Cdk1/2 activity after DNA damage promotes senescence |
title_full_unstemmed | Residual Cdk1/2 activity after DNA damage promotes senescence |
title_short | Residual Cdk1/2 activity after DNA damage promotes senescence |
title_sort | residual cdk1/2 activity after dna damage promotes senescence |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418196/ https://www.ncbi.nlm.nih.gov/pubmed/28345297 http://dx.doi.org/10.1111/acel.12588 |
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