Spatial Dynamics of Chromosome Translocations in Living Cells

• Published in: Science (American Association for the Advancement of Science) Vol. 341; no. 6146; pp. 660 - 664
• Main Authors: Roukos, Vassilis, Voss, Ty C., Schmidt, Christine K., Lee, Seungtaek, Wangsa, Darawalee, Misteli, Tom
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 09.08.2013; The American Association for the Advancement of Science
• 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
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1237150

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.