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

被引：66

作者：

Inagaki, Hidehito ^{[1
]}

Ohye, Tamae ^{[1
]}

Kogo, Hiroshi ^{[1
]}

Kato, Takema ^{[1
,2
]}

Bolor, Hasbaira ^{[2
]}

Taniguchi, Mariko ^{[1
]}

Shaikh, Tamim H. ^{[3
,4
]}

Emanuel, Beverly S. ^{[3
,4
]}

Kurahashi, Hiroki ^{[1
]}

机构：

[1] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Mol Genet, Aichi 4701192, Japan

[2] Fujita Hlth Univ, Dev Ctr Targeted & Invas Diag & Treatment, Century COE Program 21st, Aichi 4701192, Japan

[3] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[4] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

来源：

GENOME RESEARCH | 2009年 / 19卷 / 02期

关键词：

MAJOR BREAKPOINT REGION; AT-RICH REPEATS; CONSTITUTIONAL T(11/22); GENOMIC INSTABILITY; REPAIR; CELLS; GENE; COMPLEX; REARRANGEMENTS; PALINDROMES;

D O I：

10.1101/gr.079244.108

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：191 / 198

页数：8

共 43 条

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