Chromosomal instability mediated by non-B DNA: Cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans

  1. Hidehito Inagaki1,
  2. Tamae Ohye1,
  3. Hiroshi Kogo1,
  4. Takema Kato1,
  5. Hasbaira Bolor1,
  6. Mariko Taniguchi1,
  7. Tamim H Shaikh2,
  8. Beverly S Emanuel2, and
  9. Hiroki Kurahashi1,3
  1. 1 Institute for Comprehensive Medical Science, Fujita Health University;
  2. 2 University of Pennsylvania School of Medicine

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

    • Received April 1, 2008.
    • Accepted October 28, 2008.

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  1. Published in Advance November 7, 2008, doi: 10.1101/gr.079244.108 Genome Res. gr.079244.108 Copyright © 2008, Cold Spring Harbor Laboratory Press

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