Publication Date:
2012-02-09
Description:
Recurrent chromosomal translocations underlie both haematopoietic and solid tumours. Their origin has been ascribed to selection of random rearrangements, targeted DNA damage, or frequent nuclear interactions between translocation partners; however, the relative contribution of each of these elements has not been measured directly or on a large scale. Here we examine the role of nuclear architecture and frequency of DNA damage in the genesis of chromosomal translocations by measuring these parameters simultaneously in cultured mouse B lymphocytes. In the absence of recurrent DNA damage, translocations between Igh or Myc and all other genes are directly related to their contact frequency. Conversely, translocations associated with recurrent site-directed DNA damage are proportional to the rate of DNA break formation, as measured by replication protein A accumulation at the site of damage. Thus, non-targeted rearrangements reflect nuclear organization whereas DNA break formation governs the location and frequency of recurrent translocations, including those driving B-cell malignancies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459314/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459314/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hakim, Ofir -- Resch, Wolfgang -- Yamane, Arito -- Klein, Isaac -- Kieffer-Kwon, Kyong-Rim -- Jankovic, Mila -- Oliveira, Thiago -- Bothmer, Anne -- Voss, Ty C -- Ansarah-Sobrinho, Camilo -- Mathe, Ewy -- Liang, Genqing -- Cobell, Jesse -- Nakahashi, Hirotaka -- Robbiani, Davide F -- Nussenzweig, Andre -- Hager, Gordon L -- Nussenzweig, Michel C -- Casellas, Rafael -- AI037526/AI/NIAID NIH HHS/ -- R01 AI037526/AI/NIAID NIH HHS/ -- Z01 AR041148-03/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 7;484(7392):69-74. doi: 10.1038/nature10909.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Receptor Biology and Gene Expression, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22314321" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
B-Lymphocytes/cytology/*metabolism/*pathology
;
Cell Nucleus/genetics/metabolism
;
Cells, Cultured
;
Chromosome Positioning
;
Chromosomes, Mammalian/genetics/metabolism
;
Cytidine Deaminase/deficiency/genetics/metabolism
;
DNA Breaks, Double-Stranded
;
DNA Damage/*genetics
;
Genes, myc/genetics
;
Genome/genetics
;
Immunoglobulin Heavy Chains/genetics
;
Mice
;
Replication Protein A/metabolism
;
Translocation, Genetic/*genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink