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 Kato12,
  5. Hasbaira Bolor2,
  6. Mariko Taniguchi14,
  7. Tamim H. Shaikh3,
  8. Beverly S. Emanuel3 and
  9. Hiroki Kurahashi15
  1. 1Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan
  2. 221st Century COE Program, Development Center for Targeted and Invasive Diagnosis and Treatment, Fujita Health University, Toyoake, Aichi 470-1192, Japan
  3. 3Division of Human Genetics, The Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA

    Abstract

    Chromosomal aberrations have been thought to be random events. However, recent findings introduce a new paradigm in which certain DNA segments have the potential to adopt unusual conformations that lead to genomic instability and nonrandom 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 intermolecular 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 that confer a common pathway for chromosomal rearrangements in humans.

    Footnotes

    • ↵ Present address: Division of Functional Genomics, Department of Post-Genomics and Diseases, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.

    • ↵ Corresponding author.

      ↵ E-mail kura{at}fujita-hu.ac.jp; fax 81-562-93-8831.

    • [Supplemental material is available online at www.genome.org.]

    • Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.079244.108.

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

    This Article

    1. Published in Advance November 7, 2008, doi: 10.1101/gr.079244.108 Genome Res. Copyright © 2009 by Cold Spring Harbor Laboratory Press

    Article Category

    Share

    Preprint Server



    Current Issue

    1. January 2026, 36 (1)
    1. Current Issue
    1. Alert me to new issues of Genome Research