Spatial Dynamics of Chromosome Translocations in Living Cells

Chromosome translocations are a hallmark of cancer cells. We have developed an experimental system to visualize the formation of translocations in living cells and apply it to characterize the spatial and dynamic properties of translocation formation. We demonstrate that translocations form within h...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-08, Vol.341 (6146), p.660-664
Main Authors: Roukos, Vassilis, Voss, Ty C., Schmidt, Christine K., Lee, Seungtaek, Wangsa, Darawalee, Misteli, Tom
Format: Article
Language:English
Subjects:
Animals
B lymphocytes
Bacterial Proteins - genetics
Break in
Cancer
Carrier Proteins - genetics
Cell Cycle
Cells
Cells (biology)
Cellular biology
Chromosome translocation
Chromosomes
Culture
Deoxyribonucleic acid
DNA Breaks, Double-Stranded
DNA Repair
DNA-Activated Protein Kinase - antagonists & inhibitors
DNA-Binding Proteins - antagonists & inhibitors
Green Fluorescent Proteins - genetics
High-Throughput Screening Assays
Lac Operon
Lac Repressors - genetics
Merging
Mice
Microscopy
Microscopy - methods
Movies
Neoplasms - genetics
NIH 3T3 Cells
Nuclear Proteins - antagonists & inhibitors
Polymerase chain reaction
Proteins
Proximity
Repair
Small interfering RNA
Time-Lapse Imaging
Translocation, Genetic
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Summary:Chromosome translocations are a hallmark of cancer cells. We have developed an experimental system to visualize the formation of translocations in living cells and apply it to characterize the spatial and dynamic properties of translocation formation. We demonstrate that translocations form within hours of the occurrence of double-strand breaks (DSBs) and that their formation is cell cycle—independent. Translocations form preferentially between prepositioned genome elements, and perturbation of key factors of the DNA repair machinery uncouples DSB pairing from translocation formation. These observations generate a spatiotemporal framework for the formation of translocations in living cells.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1237150