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

Hidehito Inagaki, Tamae Ohye, Hiroshi Kogo, Takema Kato, Hasbaira Bolor, Mariko Taniguchi, Tamim H. Shaikh, Beverly S. Emanuel, Hiroki Kurahashi

Research output: Contribution to journalArticle

51 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)191-198
Number of pages8
JournalGenome Research
Volume19
Issue number2
DOIs
Publication statusPublished - 01-02-2009

Fingerprint

Cruciform DNA
Nucleic Acid Conformation
Chromosomal Instability
Plasmids
Genomic Instability
HEK293 Cells
Chromosome Aberrations
DNA

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

@article{eb142b3ee814474bafff83d90cad1db7,
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.",
author = "Hidehito Inagaki and Tamae Ohye and Hiroshi Kogo and Takema Kato and Hasbaira Bolor and Mariko Taniguchi and Shaikh, {Tamim H.} and Emanuel, {Beverly S.} and Hiroki Kurahashi",
year = "2009",
month = "2",
day = "1",
doi = "10.1101/gr.079244.108",
language = "English",
volume = "19",
pages = "191--198",
journal = "Genome Research",
issn = "1088-9051",
publisher = "Cold Spring Harbor Laboratory Press",
number = "2",

}

Chromosomal instability mediated by non-B DNA : Cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans. / Inagaki, Hidehito; Ohye, Tamae; Kogo, Hiroshi; Kato, Takema; Bolor, Hasbaira; Taniguchi, Mariko; Shaikh, Tamim H.; Emanuel, Beverly S.; Kurahashi, Hiroki.

In: Genome Research, Vol. 19, No. 2, 01.02.2009, p. 191-198.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chromosomal instability mediated by non-B DNA

T2 - Cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans

AU - Inagaki, Hidehito

AU - Ohye, Tamae

AU - Kogo, Hiroshi

AU - Kato, Takema

AU - Bolor, Hasbaira

AU - Taniguchi, Mariko

AU - Shaikh, Tamim H.

AU - Emanuel, Beverly S.

AU - Kurahashi, Hiroki

PY - 2009/2/1

Y1 - 2009/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=59949101230&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59949101230&partnerID=8YFLogxK

U2 - 10.1101/gr.079244.108

DO - 10.1101/gr.079244.108

M3 - Article

C2 - 18997000

AN - SCOPUS:59949101230

VL - 19

SP - 191

EP - 198

JO - Genome Research

JF - Genome Research

SN - 1088-9051

IS - 2

ER -