Chromosomal Instability Mediated by Non-B DNA: Cruciform Conformation and Not DNA Sequence is Responsible for Recurrent Translocation in Humans

Overview

Journal Genome Res

Specialty Genetics

Date 2008 Nov 11

PMID 18997000

Citations 48

Authors

Hidehito Inagaki

Tamae Ohye

Hiroshi Kogo

Takema Kato

Hasbaira Bolor

Mariko Taniguchi

Tamim H Shaikh

Beverly S Emanuel

Hiroki Kurahashi

Affiliations

Soon will be listed here.

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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