Chromosome neighborhood composition determines translocation outcomes after exposure to high-dose radiation in primary cells Export

@article{citeulike:2859168, abstract = {Abstract\ \ Radiation exposure is an occupational hazard for military personnel, some health care professionals, airport security screeners, and medical patients, with some individuals at risk for acute, high-dose exposures. Therefore, the biological effects of radiation, especially the potential for chromosome damage, are major occupational and health concerns. However, the biophysical mechanisms of chromosome instability subsequent to radiation-induced DNA damage are poorly understood. It is clear that interphase chromosomes occupy discrete structural and functional subnuclear domains, termed chromosome territories (CT), which may be organized into 'neighborhoods' comprising groups of specific CTs. We directly evaluated the relationship between chromosome positioning, neighborhood composition, and translocation partner choice in primary lymphocytes, using a cell-based system in which we could induce multiple, concentrated DNA breaks via high-dose irradiation. We critically evaluated mis-rejoining profiles and tested whether breaks occurring nearby were more likely to fuse than breaks occurring at a distance. We show that CT neighborhoods comprise heterologous chromosomes, within which inter-CT distances directly relate to translocation partner choice. These findings demonstrate that interphase chromosome arrangement is a principal factor in genomic instability outcomes in primary lymphocytes, providing a structural context for understanding the biological effects of radiation exposure, and the molecular etiology of tumor-specific translocation patterns.}, author = {Brianna and Grant, Jeremy and Szatkiewicz, Jin and van Hase, Johann and Shirley, Bobbi-Jo and Bewersdorf, Joerg and Cremer, Christoph and Arneodo, Alain and Khalil, Andre and Mills, Kevin}, citeulike-article-id = {2859168}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s10577-007-1181-7}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18060570}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18060570}, day = {4}, doi = {10.1007/s10577-007-1181-7}, journal = {Chromosome Research}, keywords = {chromosome, mechanisms, mice, translocation}, month = {December}, number = {8}, pages = {1061--1073}, posted-at = {2008-06-03 15:09:55}, priority = {3}, title = {Chromosome neighborhood composition determines translocation outcomes after exposure to high-dose radiation in primary cells}, url = {http://dx.doi.org/10.1007/s10577-007-1181-7}, volume = {15}, year = {2007} }

TY - JOUR ID - citeulike:2859168 L3 - citeulike-article-id:2859168 N2 - Abstract  Radiation exposure is an occupational hazard for military personnel, some health care professionals, airport security screeners, and medical patients, with some individuals at risk for acute, high-dose exposures. Therefore, the biological effects of radiation, especially the potential for chromosome damage, are major occupational and health concerns. However, the biophysical mechanisms of chromosome instability subsequent to radiation-induced DNA damage are poorly understood. It is clear that interphase chromosomes occupy discrete structural and functional subnuclear domains, termed chromosome territories (CT), which may be organized into ‘neighborhoods’ comprising groups of specific CTs. We directly evaluated the relationship between chromosome positioning, neighborhood composition, and translocation partner choice in primary lymphocytes, using a cell-based system in which we could induce multiple, concentrated DNA breaks via high-dose irradiation. We critically evaluated mis-rejoining profiles and tested whether breaks occurring nearby were more likely to fuse than breaks occurring at a distance. We show that CT neighborhoods comprise heterologous chromosomes, within which inter-CT distances directly relate to translocation partner choice. These findings demonstrate that interphase chromosome arrangement is a principal factor in genomic instability outcomes in primary lymphocytes, providing a structural context for understanding the biological effects of radiation exposure, and the molecular etiology of tumor-specific translocation patterns. IS - 8 JF - Chromosome Research EP - 1073 TI - Chromosome neighborhood composition determines translocation outcomes after exposure to high-dose radiation in primary cells VL - 15 SP - 1061 KW - chromosome KW - mechanisms KW - mice KW - translocation AU - Brianna AU - Grant, Jeremy AU - Szatkiewicz, Jin AU - van Hase, Johann AU - Shirley, Bobbi-Jo AU - Bewersdorf, Joerg AU - Cremer, Christoph AU - Arneodo, Alain AU - Khalil, Andre AU - Mills, Kevin PY - 2007/12/04/ UR - http://dx.doi.org/10.1007/s10577-007-1181-7 ER -