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

    • 1 Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan;
    • 2 21st Century COE Program, Development Center for Targeted and Invasive Diagnosis and Treatment, Fujita Health University, Toyoake, Aichi 470-1192, Japan;
    • 3 Division of Human Genetics, The Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    • 4 Present address: Division of Functional Genomics, Department of Post-Genomics and Diseases, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
    • 5 Corresponding author. E-mail [email protected]; fax 81-562-93-8831.
Published November 7, 2008. Vol 19 Issue 2, pp. 191-198. https://doi.org/10.1101/gr.079244.108
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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.

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