Chromosomal instability mediated by non-B DNA: cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans.
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.
Inagaki
Hidehito
H
Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
Ohye
Tamae
T
Kogo
Hiroshi
H
Kato
Takema
T
Bolor
Hasbaira
H
Taniguchi
Mariko
M
Shaikh
Tamim H
TH
Emanuel
Beverly S
BS
Kurahashi
Hiroki
H
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*
D004270:DNA, Circular