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Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations.

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Affiliations

  • 1. Department of Medical Oncology and Cancer Genomics Center, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands.
      Authors
    • Janssen A 1
    (1 author)

ORCIDs linked to this article

Science, 01 Sep 2011, 333(6051):1895-1898
https://doi.org/10.1126/science.1210214 PMID: 21960636 

Abstract 

Various types of chromosomal aberrations, including numerical (aneuploidy) and structural (e.g., translocations, deletions), are commonly found in human tumors and are linked to tumorigenesis. Aneuploidy is a direct consequence of chromosome segregation errors in mitosis, whereas structural aberrations are caused by improperly repaired DNA breaks. Here, we demonstrate that chromosome segregation errors can also result in structural chromosome aberrations. Chromosomes that missegregate are frequently damaged during cytokinesis, triggering a DNA double-strand break response in the respective daughter cells involving ATM, Chk2, and p53. We show that these double-strand breaks can lead to unbalanced translocations in the daughter cells. Our data show that segregation errors can cause translocations and provide insights into the role of whole-chromosome instability in tumorigenesis.

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Read article at publisher's site: https://doi.org/10.1126/science.1210214

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Funding 

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European Research Council (1)