Related Experiment Video
Updated: Mar 10, 2026
Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
Profiling DNA damage response following mitotic perturbations
Ronni S Pedersen1, Gopal Karemore1, Thorkell Gudjonsson1
1Protein Signaling Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
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.
Insights
Mitotic errors can cause DNA breakage in daughter cells. Replication stress may limit the proliferation of cells with abnormal karyotypes, impacting genome integrity.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Genome integrity is crucial, maintained by coordinated DNA replication and chromosome segregation.
- While replication stress is well-studied, the impact of mitotic errors on genome integrity is less understood.
Purpose of the Study:
- To investigate the link between mitotic perturbations and DNA damage in daughter cells.
- To identify genuine mitosis-born DNA damage events and their functional consequences.
- To explore the role of replication stress in cells with abnormal karyotypes.
Main Methods:
- Knockdown of 47 validated mitotic regulators.
- Analysis of DNA breakage in daughter cells following mitotic errors.
- Assessment of replication stress dynamics and proliferation rates.
Main Results:
- A broad spectrum of mitotic errors correlates with increased DNA breakage.
- Only a subset of these correlations are functionally linked.
- DNA breakage after cytokinesis failure is preceded by accumulating replication stress.
- Replication stress coincides with decreased cell proliferation.
Conclusions:
- Mitotic aberrations lead to DNA breakage, with specific events identified.
- Replication stress may act as a barrier to the propagation of cells with abnormal karyotypes.
- This study provides a resource for assessing DNA damage dynamics associated with mitotic errors.
More Related Videos
Related Concept Videos
02:36DNA Damage Can Stall the Cell Cycle
02:36DNA Damage can Stall the Cell Cycle
02:04Fixing Double-strand Breaks
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:08Nucleotide Excision Repair
02:31Homologous Recombination