Modeling oncogenic translocations: Distinct roles for double-strand break repair pathways in translocation formation in mammalian cells Journal Article


Authors: Weinstock, D. M.; Richardson, C. A.; Elliott, B.; Jasin, M.
Article Title: Modeling oncogenic translocations: Distinct roles for double-strand break repair pathways in translocation formation in mammalian cells
Abstract: Reciprocal chromosomal translocations are implicated in the etiology of many tumors, including leukemias, lymphomas, and sarcomas. DNA double-strand breaks (DSBs) caused by various cellular processes and exogenous agents are thought to be responsible for the generation of most translocations. Mammalian cells have multiple pathways for repairing DSBs in the chromosomes: non-homologous end-joining (NHEJ), homologous recombination (HR), and single-strand annealing (SSA), which is a specialized pathway involving sequence repeats. In this review, we summarize the various reporters that have been used to examine the potential for each of these DSB repair pathways to mediate translocation formation in mammalian cells. This approach has demonstrated that NHEJ is very proficient at mediating translocation formation, while HR is not because of crossover suppression. Although SSA can efficiently mediate translocations between identical repeats, its contribution to translocation formation is likely very limited because of sequence divergence between repetitive elements in the genome. © 2006 Elsevier B.V. All rights reserved.
Keywords: leukemia; acute granulocytic leukemia; gene mutation; gene sequence; gene translocation; gene deletion; nonhuman; neoplasms; mammalia; animals; dna damage; gene; homologous recombination; dna repair; gene expression; gene locus; intron; gene frequency; tumor cells, cultured; carcinogenesis; dna strand breakage; sarcoma; fluorescence in situ hybridization; statistical significance; double stranded dna; dna modification; recombination, genetic; lymphoma; chromosome breakage; chromosome translocation; translocation, genetic; genome; models, genetic; genes, reporter; genomic dna; double-strand breaks; translocation; non homologous end joining; single-strand annealing; chromosomes, mammalian; nonhomologous end-joining; alu sequence; alu elements
Journal Title: DNA Repair
Volume: 5
Issue: 9-10
ISSN: 1568-7864
Publisher: Elsevier Inc.  
Date Published: 2006-09-08
Start Page: 1065
End Page: 1074
Language: English
DOI: 10.1016/j.dnarep.2006.05.028
PUBMED: 16815104
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 73" - "Export Date: 4 June 2012" - "CODEN: DRNEA" - "Source: Scopus"
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  1. Maria Jasin
    249 Jasin