Chromosomal instability mediated by non-B DNA: Cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans
Abstract
Chromosomal aberrations have been thought to be random events. However, recent findings introduce a new paradigm that certain DNA segments have the potential to adopt unusual conformations that lead to genomic instability and non-random chromosomal rearrangement. One of the best-studied examples is the palindromic AT-rich repeat (PATRR), which induces recurrent constitutional translocations in humans. Here, we established a plasmid-based model that promotes frequent inter-molecular rearrangements between two PATRRs in HEK293 cells. In this model system, the proportion of PATRR plasmid that extrudes a cruciform structure correlates to the levels of rearrangement. Our data suggest that PATRR-mediated translocations are attributable to unusual DNA conformations, which confer a common pathway for chromosomal rearrangements in humans.
Footnotes
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- Received April 1, 2008.
- Accepted October 28, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
