1. Cell Biology
  2. Chromosomes and Gene Expression
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Chromosome territory formation attenuates the translocation potential of cells

  1. Leah F Rosin
  2. Olivia Crocker
  3. Randi L Isenhart
  4. Son C Nguyen
  5. Zhuxuan Xu
  6. Eric F Joyce  Is a corresponding author
  1. University of Pennsylvania, United States
Research Article
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Cite this article as: eLife 2019;8:e49553 doi: 10.7554/eLife.49553

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.

Article and author information

Author details

  1. Leah F Rosin

    Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2489-4016
  2. Olivia Crocker

    Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Randi L Isenhart

    Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Son C Nguyen

    Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Zhuxuan Xu

    Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Eric F Joyce

    Department of Genetics, University of Pennsylvania, Philadelphia, United States
    For correspondence
    erjoyce@upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0418-2804

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.

Reviewing Editor

  1. Abby F Dernburg, UC Berkeley and HHMI, United States

Publication history

  1. Received: June 20, 2019
  2. Accepted: November 2, 2019
  3. Accepted Manuscript published: November 4, 2019 (version 1)

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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