Cited by 491DNA Repair MechanismsGenomics and Chromatin DynamicsGenomic variations and chromosomal abnormalities

Dynamics of DNA Double-Strand Breaks Revealed by Clustering of Damaged Chromosome Domains

Aten, Jacob A., Stap, Jan, Krawczyk, Przemek M., van Oven, Carel H., Hoebe, Ron A., Essers, Jeroen, Kanaar, Roland·2004·Science

Abstract

Interactions between ends from different DNA double-strand breaks (DSBs) can produce tumorigenic chromosome translocations. Two theories for the juxta-position of DSBs in translocations, the static "contact-first" and the dynamic "breakage-first" theory, differ fundamentally in their requirement for DSB mobility. To determine whether or not DSB-containing chromosome domains are mobile and can interact, we introduced linear tracks of DSBs in nuclei. We observed changes in track morphology within minutes after DSB induction, indicating movement of the domains. In a subpopulation of cells, the domains clustered. Juxtaposition of different DSB-containing chromosome domains through clustering, which was most extensive in G1 phase cells, suggests an adhesion process in which we implicate the Mre11 complex. Our results support the breakage-first theory to explain the origin of chromosomal translocations.

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Crossref · 10.1126/science.1088845

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Authors
Aten, J. A., Stap, J., Krawczyk, P. M., van Oven, C. H., Hoebe, R. A., Essers, J., & Kanaar, R.
Affiliations
  • Erasmus MC (NL)
  • Center for Microscopical Research, Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, Netherlands.
Corresponding author
Kanaar, Roland
Venue
Science
Published
2004-01-02
Volume
303
Issue
5654
Pages
92-95
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2041251646
Cited by
491
References
21
Citations by year
2026: 5 · 2025: 14 · 2024: 11 · 2023: 18 · 2022: 12 · 2021: 23 · 2020: 18 · 2019: 17 · 2018: 26 · 2017: 26 · 2016: 16 · 2015: 17 · 2014: 22 · 2013: 26 · 2012: 24
FWCI
13.14
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
DNA double-strand breaks, chromosomal translocation, Mre11 complex, G1 phase, carcinogenesis
MeSH terms
MRE11 Homologue Protein, Alpha Particles, Animals, Ataxia Telangiectasia, Cell Nucleus, Chromosomes, Human, Cricetulus, DNA, DNA Damage, DNA Repair, DNA-Binding Proteins, Fibroblasts, Cricetinae, HeLa Cells, Histones, Humans, Phosphorylation, Translocation, Genetic, G1 Phase, G2 Phase, S Phase, CHO Cells, Chromosome Breakage, Chromosomes, Mammalian, Rad51 Recombinase

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