title: 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 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.
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Inagaki
authors.forename: Tamae
authors.initials: T
authors.lastname: Ohye
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kogo
authors.forename: Takema
authors.initials: T
authors.lastname: Kato
authors.forename: Hasbaira
authors.initials: H
authors.lastname: Bolor
authors.forename: Mariko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Tamim H
authors.initials: TH
authors.lastname: Shaikh
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Emanuel
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
mesh_terms: D001483:Base Sequence / Q000502:physiology*; D002478:Cells, Cultured; D043171:Chromosomal Instability / Q000235:genetics*; D004270:DNA, Circular / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D055029:Inverted Repeat Sequences / Q000235:genetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000737:chemistry; D012008:Recurrence; D012689:Sequence Homology, Nucleic Acid; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D004270:DNA, Circular