Generation of Gross Chromosomal Rearrangements by a Single Engineered DNA Double Strand Break
| Autor: | Peter D. Aplan, Zhenhua Zhang, Zhijun Qiu, Tamas Varga, Anna V. Roschke |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Dna dsbs cells Chromosomal translocation Article Chromosomes Malignant transformation Cell Line Histones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Humans DNA Breaks Double-Stranded Double strand Genetics Gene Rearrangement Gene knockdown Multidisciplinary Chemistry fungi Gene rearrangement Fibroblasts Cell biology enzymes and coenzymes (carbohydrates) 030104 developmental biology Cell culture 030220 oncology & carcinogenesis biological phenomena cell phenomena and immunity DNA |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep43156 |
| Popis: | Gross chromosomal rearrangements (GCRs), including translocations, inversions amplifications, and deletions, can be causal events leading to malignant transformation. GCRs are thought to be triggered by DNA double strand breaks (DSBs), which in turn can be spontaneous or induced by external agents (eg. cytotoxic chemotherapy, ionizing radiation). It has been shown that induction of DNA DSBs at two defined loci can produce stable balanced chromosomal translocations, however, a single engineered DNA DSB could not. Herein, we report that although a single engineered DNA DSB in H2AX “knockdown” cells did not generate GCRs, repair of a single engineered DNA DSB in fibroblasts that had ablated H2ax did produce clonal, stable GCRs, including balanced translocations and megabase-pair inversions. Upon correction of the H2ax deficiency, cells no longer generated GCRs following a single engineered DNA DSB. These findings demonstrate that clonal, stable GCRs can be produced by a single engineered DNA DSB in H2ax knockout cells, and that the production of these GCRs is ameliorated by H2ax expression. |
| Databáze: | OpenAIRE |
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