Chromosome territory formation attenuates the translocation potential of cells
- University of Pennsylvania, United States
Abstract
The formation and spatial arrangement of chromosome territories (CTs) during interphase has been posited to influence the outcome and frequency of genomic translocations. This is supported by correlations between the frequency of inter-chromosomal contacts and translocation events in myriad systems. However, it remains unclear if CT formation itself influences the translocation potential of cells. We address this question in Drosophila cells by modulating the level of Condensin II, which regulates CT organization. Using whole-chromosome Oligopaints to identify genomic rearrangements, we find that increased contact frequencies between chromosomes due to Condensin II knockdown leads to an increased propensity to form translocations following DNA damage. Moreover, Condensin II over-expression is sufficient to drive spatial separation of CTs and attenuate the translocation potential of cells. Together, these results provide the first causal evidence that proper CT formation can protect the genome from potentially deleterious translocations in the presence of DNA damage.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
Pittsburgh Foundation (KA2017-91787)
- Eric F Joyce
National Institute of General Medical Sciences (R35GM128903)
- Eric F Joyce
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Rosin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Chromosome territory formation attenuates the translocation potential of cells
eLife 8:e49553.
https://doi.org/10.7554/eLife.49553
