Pedersen, RS;
Karemore, G;
Gudjonsson, T;
Rask, M-B;
Neumann, B;
Heriche, J-K;
Pepperkok, R;
... Lukas, C; + view all
(2016)
Profiling DNA damage response following mitotic perturbations.
Nature Communications
, 7
, Article 13887. 10.1038/ncomms13887.
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Abstract
Genome integrity relies on precise coordination between DNA replication and chromosome segregation. Whereas replication stress attracted much attention, the consequences of mitotic perturbations for genome integrity are less understood. Here, we knockdown 47 validated mitotic regulators to show that a broad spectrum of mitotic errors correlates with increased DNA breakage in daughter cells. Unexpectedly, we find that only a subset of these correlations are functionally linked. We identify the genuine mitosis-born DNA damage events and sub-classify them according to penetrance of the observed phenotypes. To demonstrate the potential of this resource, we show that DNA breakage after cytokinesis failure is preceded by replication stress, which mounts during consecutive cell cycles and coincides with decreased proliferation. Together, our results provide a resource to gauge the magnitude and dynamics of DNA breakage associated with mitotic aberrations and suggest that replication stress might limit propagation of cells with abnormal karyotypes.
| Type: | Article |
|---|---|
| Title: | Profiling DNA damage response following mitotic perturbations |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncomms13887 |
| Publisher version: | https://doi.org/10.1038/ncomms13887 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, REPLICATION STRESS, CYTOKINESIS FAILURE, GENOME STABILITY, CHROMOSOME SEGREGATION, ABNORMAL MITOSIS, CELL-DIVISION, CANCER, INSTABILITY, CHECKPOINT, 53BP1 |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10038502 |
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