Chromosomal instability mediated by non-B DNA: Cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans
Chromosomal instability mediated by non-B DNA: Cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans
复制标题
DOI：
10.1101/gr.079244.108
复制
发表时间：
2009-02-01
期刊：
影响因子：
7
通讯作者：
Kurahashi, Hiroki
中科院分区：
文献类型：
--
作者：
Inagaki, Hidehito;Ohye, Tamae;Kurahashi, Hiroki
染色体畸变被认为是随机事件。然而，最近的研究结果引入了一种新的范式，其中某些 DNA 片段有可能采用不寻常的构象，从而导致基因组不稳定和非随机染色体重排。研究最好的例子之一是富含 AT 的回文重复序列 (PATRR)，它会在人类中诱导反复的体质易位。在这里，我们建立了一个基于质粒的模型，该模型促进 HEK293 细胞中两个 PATRR 之间频繁的分子间重排。在该模型系统中，挤出十字形结构的 PATRR 质粒的比例与重排水平相关。我们的数据表明，PATRR 介导的易位可归因于不寻常的 DNA 构象，这些构象为人类染色体重排提供了共同的途径。
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.