Palindrome-mediated chromosomal translocations in humans
Palindrome-mediated chromosomal translocations in humans
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DOI：
10.1016/j.dnarep.2006.05.035
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发表时间：
2006-09-08
期刊：
影响因子：
3.8
通讯作者：
Emanuel, Beverly S.
中科院分区：
文献类型：
--
作者：
Kurahashi, Hiroki;Inagaki, Hidehito;Emanuel, Beverly S.
最近，回文介导的基因组不稳定性导致了一组不同的基因组重排，包括易位、缺失和扩增。最好的研究例子之一是人类中反复发生的t(11；22)结构性易位，已有充分的证据表明，这种易位是由染色体11q23和22q11上的富含回文的AT重复序列(PATRR)介导的。这种易位的新例子在正常健康男性的精子样本中检测到的频率很高，但在淋巴母细胞或成纤维细胞中检测不到。克隆的断点序列在体外优先形成十字形构型。对连接片段的分析表明，在两个回文区域的中心经常发生双链断裂(DSB)，随后通过非同源末端连接(NHEJ)途径进行修复。我们认为PATRR在雄性减数分裂细胞中采用十字形结构，造成基因组不稳定，导致反复易位。(C)2006爱思唯尔B.V.保留所有权利。
Recently, it has emerged that palindrome-mediated genomic instability contributes to a diverse group of genomic rearrangements including translocations, deletions, and amplifications. One of the best studied examples is the recurrent t(11;22) constitutional translocation in humans that has been well documented to be mediated by palindromic AT-rich repeats (PATRRs) on chromosomes 11q23 and 22q11. De novo examples of the translocation are detected at a high frequency in sperm samples from normal healthy males, but not in lymphoblasts or fibroblasts. Cloned breakpoint sequences preferentially form a cruciform configuration in vitro. Analysis of the junction fragments implicates frequent double-strandbreaks (DSBs) at the center of both palindromic regions, followed by repair through the non-homologous end joining (NHEJ) pathway. We propose that the PATRR adopts a cruciform structure in male meiotic cells, creating genomic instability that leads to the recurrent translocation. (c) 2006 Elsevier B.V. All rights reserved.