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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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Published in: | Science (American Association for the Advancement of Science) 2013-08, Vol.341 (6146), p.660-664 |
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creator | Roukos, Vassilis Voss, Ty C. Schmidt, Christine K. Lee, Seungtaek Wangsa, Darawalee Misteli, Tom |
description | 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. |
doi_str_mv | 10.1126/science.1237150 |
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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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1237150</identifier><identifier>PMID: 23929981</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>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</subject><ispartof>Science (American Association for the Advancement of Science), 2013-08, Vol.341 (6146), p.660-664</ispartof><rights>Copyright © 2013 American Association for the Advancement of Science</rights><rights>Copyright © 2013, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c575t-7cde81d8e3ea59a41f5daf13b6009f6e4b1fb42efb93b6e69be1beda9401d8023</citedby><cites>FETCH-LOGICAL-c575t-7cde81d8e3ea59a41f5daf13b6009f6e4b1fb42efb93b6e69be1beda9401d8023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/23491300$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/23491300$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,885,2884,2885,27924,27925,58238,58471</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23929981$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Roukos, Vassilis</creatorcontrib><creatorcontrib>Voss, Ty C.</creatorcontrib><creatorcontrib>Schmidt, Christine K.</creatorcontrib><creatorcontrib>Lee, Seungtaek</creatorcontrib><creatorcontrib>Wangsa, Darawalee</creatorcontrib><creatorcontrib>Misteli, Tom</creatorcontrib><title>Spatial Dynamics of Chromosome Translocations in Living Cells</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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.</description><subject>Animals</subject><subject>B lymphocytes</subject><subject>Bacterial Proteins - genetics</subject><subject>Break in</subject><subject>Cancer</subject><subject>Carrier Proteins - genetics</subject><subject>Cell Cycle</subject><subject>Cells</subject><subject>Cells (biology)</subject><subject>Cellular biology</subject><subject>Chromosome translocation</subject><subject>Chromosomes</subject><subject>Culture</subject><subject>Deoxyribonucleic acid</subject><subject>DNA Breaks, Double-Stranded</subject><subject>DNA Repair</subject><subject>DNA-Activated Protein Kinase - antagonists & inhibitors</subject><subject>DNA-Binding Proteins - antagonists & inhibitors</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>High-Throughput Screening Assays</subject><subject>Lac Operon</subject><subject>Lac Repressors - genetics</subject><subject>Merging</subject><subject>Mice</subject><subject>Microscopy</subject><subject>Microscopy - methods</subject><subject>Movies</subject><subject>Neoplasms - genetics</subject><subject>NIH 3T3 Cells</subject><subject>Nuclear Proteins - antagonists & inhibitors</subject><subject>Polymerase chain reaction</subject><subject>Proteins</subject><subject>Proximity</subject><subject>Repair</subject><subject>Small interfering RNA</subject><subject>Time-Lapse Imaging</subject><subject>Translocation, Genetic</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqFkUFr3DAQhUVpaTZpzz01GHLJxYlGsmTp0EDYJmlhoYemZyHL40SLLW0kbyD_viq7CWkvPQ3M--YxM4-QT0DPAJg8z85jcHgGjLcg6BuyAKpFrRnlb8mCUi5rRVtxQA5zXlNaNM3fkwPGNdNawYJ8-bmxs7dj9fUp2Mm7XMWhWt6nOMUcJ6xukw15jK5AMeTKh2rlH324q5Y4jvkDeTfYMePHfT0iv66vbpff6tWPm-_Ly1XtRCvmunU9KugVcrRC2wYG0dsBeCfLRoPEpoOhaxgOnS49lLpD6LC3uqFlijJ-RC52vpttN2HvMMzJjmaT_GTTk4nWm7-V4O_NXXw0krNGM1UMTvcGKT5sMc9m8tmVE2zAuM0GFFVUUpD0_6iQUonyYFnQk3_QddymUD5hoAHVgmIUCnW-o1yKOSccXvYGav6kaPYpmn2KZeL49bkv_HNsBfi8A9Z5jumV3mjgJfXfJ9Wjow</recordid><startdate>20130809</startdate><enddate>20130809</enddate><creator>Roukos, Vassilis</creator><creator>Voss, Ty C.</creator><creator>Schmidt, Christine K.</creator><creator>Lee, Seungtaek</creator><creator>Wangsa, Darawalee</creator><creator>Misteli, Tom</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20130809</creationdate><title>Spatial Dynamics of Chromosome Translocations in Living Cells</title><author>Roukos, Vassilis ; Voss, Ty C. ; Schmidt, Christine K. ; Lee, Seungtaek ; Wangsa, Darawalee ; Misteli, Tom</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c575t-7cde81d8e3ea59a41f5daf13b6009f6e4b1fb42efb93b6e69be1beda9401d8023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>B lymphocytes</topic><topic>Bacterial Proteins - genetics</topic><topic>Break in</topic><topic>Cancer</topic><topic>Carrier Proteins - genetics</topic><topic>Cell Cycle</topic><topic>Cells</topic><topic>Cells (biology)</topic><topic>Cellular biology</topic><topic>Chromosome translocation</topic><topic>Chromosomes</topic><topic>Culture</topic><topic>Deoxyribonucleic acid</topic><topic>DNA Breaks, Double-Stranded</topic><topic>DNA Repair</topic><topic>DNA-Activated Protein Kinase - antagonists & inhibitors</topic><topic>DNA-Binding Proteins - antagonists & inhibitors</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>High-Throughput Screening Assays</topic><topic>Lac Operon</topic><topic>Lac Repressors - genetics</topic><topic>Merging</topic><topic>Mice</topic><topic>Microscopy</topic><topic>Microscopy - methods</topic><topic>Movies</topic><topic>Neoplasms - genetics</topic><topic>NIH 3T3 Cells</topic><topic>Nuclear Proteins - antagonists & inhibitors</topic><topic>Polymerase chain reaction</topic><topic>Proteins</topic><topic>Proximity</topic><topic>Repair</topic><topic>Small interfering RNA</topic><topic>Time-Lapse Imaging</topic><topic>Translocation, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Roukos, Vassilis</creatorcontrib><creatorcontrib>Voss, Ty C.</creatorcontrib><creatorcontrib>Schmidt, Christine K.</creatorcontrib><creatorcontrib>Lee, Seungtaek</creatorcontrib><creatorcontrib>Wangsa, Darawalee</creatorcontrib><creatorcontrib>Misteli, Tom</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Roukos, Vassilis</au><au>Voss, Ty C.</au><au>Schmidt, Christine K.</au><au>Lee, Seungtaek</au><au>Wangsa, Darawalee</au><au>Misteli, Tom</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spatial Dynamics of Chromosome Translocations in Living Cells</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2013-08-09</date><risdate>2013</risdate><volume>341</volume><issue>6146</issue><spage>660</spage><epage>664</epage><pages>660-664</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Chromosome translocations are a hallmark of cancer cells. 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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 |
title | Spatial Dynamics of Chromosome Translocations in Living Cells |
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