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Mol Cell. 2005 Mar 18;17(6):885-94.

Chromosomal translocation mechanisms at intronic alu elements in mammalian cells.

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  • 1Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.

Abstract

Repetitive elements comprise nearly half of the human genome. Chromosomal rearrangements involving these elements occur in somatic and germline cells and are causative for many diseases. To begin to understand the molecular mechanisms leading to these rearrangements in mammalian cells, we developed an intron-based system to specifically induce chromosomal translocations at Alu elements, the most numerous family of repetitive elements in humans. With this system, we found that when double-strand breaks (DSBs) were introduced adjacent to identical Alu elements, translocations occurred at high frequency and predominantly arose from repair by the single-strand annealing (SSA) pathway (85%). With diverged Alu elements, translocation frequency was unaltered, yet pathway usage shifted such that nonhomologous end joining (NHEJ) predominated as the translocation pathway (93%). These results emphasize the fluidity of mammalian DSB repair pathway usage. The intron-based system is highly adaptable to addressing a number of issues regarding molecular mechanisms of genomic rearrangements in mammalian cells.

PMID:
15780943
[PubMed - indexed for MEDLINE]
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