Palindrome-mediated chromosomal translocations in humans
- 作者：Hiroki Kurahashi ; Hidehito Inagaki ; Tamae Ohye ; Hiroshi Kogo ; Takema Kato and Beverly S. Emanuel
- 关键词：Translocation ; Palindrome ; Cruciform
- 刊名：DNA Repair
- 出版年：2006
- 期刊代码：121_15687864
- 类别：ch
- 出版时间：8 September 2006
- 卷：5
- 期：9-10
- 页码：1136-1145
- 文件大小：413 K
摘要
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-strand-breaks (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.