Genomic deletions created upon LINE-1 retrotransposition
Genomic deletions created upon LINE-1 retrotransposition
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DOI：
10.1016/s0092-8674(02)00828-0
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发表时间：
2002-08-09
期刊：
影响因子：
64.5
通讯作者：
Moran, JV
中科院分区：
文献类型：
--
作者：
Gilbert, N;Lutz-Prigge, S;Moran, JV
LINE-1（L1）逆转录转座继续影响人类基因组，但对L1如何整合到DNA中知之甚少。在此，我们开发了一种基于质粒的拯救系统，并使用它从培养的人细胞中回收了37个新的L1逆转录转座事件。插入的测序揭示了通常的L1结构标志;然而，在四种情况下，反转录转座产生大的靶位点缺失。值得注意的是，其中三个导致了嵌合L1的形成，其中包含与我们工程化的L1精确融合的内源性L1的5'末端。因此，我们的数据证明了培养细胞中L1整合的多种途径，并表明L1不仅是插入诱变剂，而且其逆转录转座可导致基因组序列的显著缺失。
LINE-1 (L1) retrotransposition continues to impact the human genome, yet little is known about how L1 integrates into DNA. Here, we developed a plasmid-based rescue system and have used it to recover 37 new Ll retrotransposition events from cultured human cells. Sequencing of the insertions revealed the usual Ll structural hallmarks; however, in four instances, retrotransposition generated large target site deletions. Remarkably, three of those resulted in the formation of chimeric Lls, containing the 5' end of an endogenous L1 fused precisely to our engineered L1. Thus, our data demonstrate multiple pathways for Ll integration in cultured cells, and show that L1 is not simply an insertional mutagen, but that its retrotransposition can result in significant deletions of genomic sequence.