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 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.
National Cancer Institute, Bethesda, MD 20892, USA.
Vassilis
V
Roukos
Ty C
TC
Voss
Christine K
CK
Schmidt
Seungtaek
S
Lee
Darawalee
D
Wangsa
Tom
T
Misteli
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002453:Cell Cycle; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D049452:Green Fluorescent Proteins / Q000235:genetics; D057166:High-Throughput Screening Assays; D007763:Lac Operon; D056968:Lac Repressors / Q000235:genetics; D051379:Mice; D008853:Microscopy / Q000379:methods; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000235:genetics; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors; D059008:Time-Lapse Imaging; D014178:Translocation, Genetic
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D056968:Lac Repressors; D009687:Nuclear Proteins; C083139:Tet O resistance protein, Bacteria; D049452:Green Fluorescent Proteins; D051747:DNA-Activated Protein Kinase; C497264:Prkdc protein, mouse