A model of oncogenic rearrangements: Differences between chromosomal translocation mechanisms and simple double-strand break repair Journal Article
| Authors: | Weinstock, D. M.; Elliott, B.; Jasin, M. |
| Article Title: | A model of oncogenic rearrangements: Differences between chromosomal translocation mechanisms and simple double-strand break repair |
| Abstract: | Recurrent reciprocal translocations are present in many hematologic and mesenchymal malignancies. Because significant sequence homology is absent from translocation breakpoint junctions, nonhomologous end-joining (NHEJ) pathways of DNA repair are presumed to catalyze their formation. We developed translocation reporters for use in mammalian cells from which NHEJ events can be selected after precise chromosomal breakage. Translocations were efficiently recovered with these reporters using mouse cells, and their breakpoint junctions recapitulated findings from oncogenic translocations. Small deletions and microhomology were present in most junctions; insertions and more complex events also were observed. Thus, our reporters model features of oncogenic rearrangements in human cancer cells. A homologous sequence at a distance from the break site affected the translocation junction without substantially altering translocation frequency. Interestingly, in a direct comparison, the spectrum of translocation breakpoint junctions differed from junctions derived from repair at a single chromosomal break, providing mechanistic insight into translocation formation. © 2006 by The American Society of Hematology. |
| Keywords: | controlled study; nonhuman; animal cell; mouse; animals; mice; dna damage; dna repair; dna strand breakage; cell transformation, neoplastic; double stranded dna; gene rearrangement; recombination, genetic; cancer cell; chromosome breakage; chromosome translocation; translocation, genetic; dna sequence; sequence homology; chromosome deletion; reciprocal chromosome translocation; mammal cell; frequency analysis; chromosome insertion; human versus animal comparison; mammalian genetics |
| Journal Title: | Blood |
| Volume: | 107 |
| Issue: | 2 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2006-01-15 |
| Start Page: | 777 |
| End Page: | 780 |
| Language: | English |
| DOI: | 10.1182/blood-2005-06-2437 |
| PUBMED: | 16195334 |
| PROVIDER: | scopus |
| PMCID: | PMC1895622 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 42" - "Export Date: 4 June 2012" - "CODEN: BLOOA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work