Internal priming: an opportunistic pathway for L1 and Alu retrotransposition in hominins.
Internal priming: an opportunistic pathway for L1 and Alu retrotransposition in hominins.
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DOI：
10.1016/j.gene.2009.05.014
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发表时间：
2009-12
期刊：
影响因子：
3.5
通讯作者：
Deepa Srikanta;S. Sen;Erin M. Conlin;M. Batzer
中科院分区：
文献类型：
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作者：
Deepa Srikanta;S. Sen;Erin M. Conlin;M. Batzer
逆转录转座子，特别是Alu和L1元件，在灵长类动物基因组中的扩展特别成功。虽然这些元件中的大多数通过内切核酸酶介导的过程整合，称为靶启动逆转录，少数整合使用替代方法。在这里，我们提出了这样一个机制，我们称之为内部启动的证据，并表明，通过这种机制整合的位点是从“经典”插入质的不同。该机制的先前例子仅限于细胞培养测定，该测定表明逆转录可以在逆转录转座子整合期间在3 'poly-A尾的上游启动。为了检测这种机制是否发生在体内以及在细胞培养中，我们分析了人类基因组的内部启动事件，使用最近整合的L1和Alu元素。我们对人类基因组的检查导致了20个涉及内部引发插入的事件的恢复，这些事件在结构上不同于经典TPRT介导的插入和非经典插入。我们提出了两种可能的机制，这些内部启动位点的创建，并提供证据支持交错DNA双链断裂修复的作用。此外，我们证明，内部启动过程与染色体间的重复和插入的填料DNA。
Retrotransposons, specifically Alu and L1 elements, have been especially successful in their expansion throughout primate genomes. While most of these elements integrate through an endonuclease-mediated process termed target primed reverse transcription, a minority integrate using alternative methods. Here we present evidence for one such mechanism, which we term internal priming and demonstrate that loci integrating through this mechanism are qualitatively different from “classical” insertions. Previous examples of this mechanism are limited to cell culture assays, which show that reverse transcription can initiate upstream of the 3′ poly-A tail during retrotransposon integration. To detect whether this mechanism occurs in vivo as well as in cell culture, we have analyzed the human genome for internal priming events using recently integrated L1 and Alu elements. Our examination of the human genome resulted in the recovery of twenty events involving internal priming insertions, which are structurally distinct from both classical TPRT-mediated insertions and non-classical insertions. We suggest two possible mechanisms by which these internal priming loci are created and provide evidence supporting a role in staggered DNA double-strand break repair. Also, we demonstrate that the internal priming process is associated with inter-chromosomal duplications and the insertion of filler DNA.