Sen Shurjo K, Huang Charles T, Han Kyudong, Batzer Mark A
Department of Biological Sciences, Biological Computation and Visualization Center, Louisiana State University, Baton Rouge, LA 70803, USA.
Nucleic Acids Res. 2007;35(11):3741-51. doi: 10.1093/nar/gkm317. Epub 2007 May 21.
LINE-1 elements (L1s) are a family of highly successful retrotransposons comprising approximately 17% of the human genome, the majority of which have inserted through an endonuclease-dependent mechanism termed target-primed reverse transcription. Recent in vitro analyses suggest that in the absence of non-homologous end joining proteins, L1 elements may utilize an alternative, endonuclease-independent pathway for insertion. However, it remains unknown whether this pathway operates in vivo or in cell lines where all DNA repair mechanisms are functional. Here, we have analyzed the human genome to demonstrate that this alternative pathway for L1 insertion has been active in recent human evolution and characterized 21 loci where L1 elements have integrated without signs of endonuclease-related activity. The structural features of these loci suggest a role for this process in DNA double-strand break repair. We show that endonuclease-independent L1 insertions are structurally distinguishable from classical L1 insertion loci, and that they are associated with inter-chromosomal translocations and deletions of target genomic DNA.
LINE-1元件（L1s）是一类非常成功的逆转座子家族，约占人类基因组的17%，其中大多数是通过一种称为靶标引发逆转录的依赖核酸内切酶的机制插入的。最近的体外分析表明，在缺乏非同源末端连接蛋白的情况下，L1元件可能利用一种替代的、不依赖核酸内切酶的途径进行插入。然而，该途径是否在体内或所有DNA修复机制均起作用的细胞系中发挥作用仍不清楚。在这里，我们分析了人类基因组，以证明这种L1插入的替代途径在近代人类进化过程中是活跃的，并鉴定了21个L1元件整合的位点，这些位点没有核酸内切酶相关活性的迹象。这些位点的结构特征表明该过程在DNA双链断裂修复中起作用。我们表明，不依赖核酸内切酶的L1插入在结构上与经典的L1插入位点不同，并且它们与染色体间易位和靶标基因组DNA的缺失有关。
