Spatial Dynamics of Chromosome Translocations in Living Cells

被引:238
作者
Roukos, Vassilis [1 ]
Voss, Ty C. [2 ]
Schmidt, Christine K. [1 ]
Lee, Seungtaek [3 ]
Wangsa, Darawalee [4 ]
Misteli, Tom [1 ]
机构
[1] NCI, Bethesda, MD 20892 USA
[2] NCI, High Throughput Imaging Facil, Bethesda, MD 20892 USA
[3] PerkinElmer Hlth Sci Inc, Waltham, MA 02451 USA
[4] NCI, Genet Branch, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
DOUBLE-STRAND BREAKS; DNA-PKCS; MOBILITY; RECOMBINATION; REPAIR;
D O I
10.1126/science.1237150
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:660 / 664
页数:5
相关论文
共 16 条
[1]   Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains [J].
Aten, JA ;
Stap, J ;
Krawczyk, PM ;
van Oven, CH ;
Hoebe, RA ;
Essers, J ;
Kanaar, R .
SCIENCE, 2004, 303 (5654) :92-95
[2]   Essential Role for DNA-PKcs in DNA Double-Strand Break Repair and Apoptosis in ATM-Deficient Lymphocytes [J].
Callen, Elsa ;
Jankovic, Mila ;
Wong, Nancy ;
Zha, Shan ;
Chen, Hua-Tang ;
Difilippantonio, Simone ;
Di Virgilio, Michela ;
Heidkamp, Gordon ;
Alt, Frederick W. ;
Nussenzweig, Andre ;
Nussenzweig, Michel .
MOLECULAR CELL, 2009, 34 (03) :285-297
[3]   Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery [J].
Dion, Vincent ;
Kalck, Veronique ;
Horigome, Chihiro ;
Towbin, Benjamin D. ;
Gasser, Susan M. .
NATURE CELL BIOLOGY, 2012, 14 (05) :502-U221
[4]   A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex [J].
Dupre, Aude ;
Boyer-Chatenet, Louise ;
Sattler, Rose M. ;
Modi, Ami P. ;
Lee, Ji-Hoon ;
Nicolette, Matthew L. ;
Kopelovich, Levy ;
Jasin, Maria ;
Baer, Richard ;
Paull, Tanya T. ;
Gautier, Jean .
NATURE CHEMICAL BIOLOGY, 2008, 4 (02) :119-125
[5]   Live cell microscopy analysis of radiation-induced DNA double-strand break motion [J].
Jakob, B. ;
Splinter, J. ;
Durante, M. ;
Taucher-Schoiz, G. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (09) :3172-3177
[6]   Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks [J].
Kruhlak, MJ ;
Celeste, A ;
Dellaire, G ;
Fernandez-Capetillo, O ;
Müller, WG ;
McNally, JG ;
Bazett-Jones, DP ;
Nussenzweig, A .
JOURNAL OF CELL BIOLOGY, 2006, 172 (06) :823-834
[7]   Spatial genome organization in the formation of chromosomal translocations [J].
Meaburn, Karen J. ;
Misteli, Tom ;
Soutoglou, Evi .
SEMINARS IN CANCER BIOLOGY, 2007, 17 (01) :80-90
[8]   Increased chromosome mobility facilitates homology search during recombination [J].
Mine-Hattab, Judith ;
Rothstein, Rodney .
NATURE CELL BIOLOGY, 2012, 14 (05) :510-U136
[9]   Higher-order Genome Organization in Human Disease [J].
Misteli, Tom .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2010, 2 (08) :a000794
[10]   The impact of translocations and gene fusions on cancer causation [J].
Mitelman, Felix ;
Johansson, Bertil ;
Mertens, Fredrik .
NATURE REVIEWS CANCER, 2007, 7 (04) :233-245