Nefedova L N, Mannanova M M, Kim A I
Department of Biology, Moscow State University, Moscow, Russia.
Virus Genes. 2011 Apr;42(2):297-306. doi: 10.1007/s11262-010-0566-4. Epub 2011 Jan 8.
Integration of DNA copies in a host genome is a necessary stage in the life cycle of retroviruses and LTR-retrotransposons. There is still no clear understanding of integration specificity of retroelements into a target site. The selection of the target DNA is believed to potentially affect a number of factors such as transcriptional status, association with histones and other DNA-binding proteins, and DNA bending. The authors performed a comprehensive computer analysis of the integration specificity of Drosophila melanogaster LTR-retrotransposons and retroviruses including an analysis of the nucleotide composition of targets, terminal sequences of LTRs, and integrase sequences. A classification of LTR-retrotransposons based on the integration specificity was developed. All the LTR-retrotransposons of the gypsy group with three open frames (errantiviruses) and their derivatives with two open frames demonstrate strict specificity to a target DNA selection. Such specificity correlates with the structural features of the target DNA: bendability, A-philicity, or protein-induced deformability. The remaining LTR-retrotransposons (copia and BEL groups, blastopia and 412 subgroups of the gypsy group) do not show specificity of integration. Chromodomain is present in the integrase structures of blastopia and 412 subgroup LTR-retrotransposons and may facilitate the process of non-specific integration.
DNA拷贝整合到宿主基因组中是逆转录病毒和LTR-逆转座子生命周期中的一个必要阶段。目前对于逆转元件整合到靶位点的特异性仍没有清晰的认识。人们认为靶DNA的选择可能会影响许多因素,如转录状态、与组蛋白和其他DNA结合蛋白的关联以及DNA弯曲。作者对黑腹果蝇LTR-逆转座子和逆转录病毒的整合特异性进行了全面的计算机分析,包括对靶标核苷酸组成、LTR末端序列和整合酶序列的分析。基于整合特异性开发了一种LTR-逆转座子分类方法。具有三个开放阅读框的吉普赛族所有LTR-逆转座子(漫游病毒)及其具有两个开放阅读框的衍生物对靶DNA选择表现出严格的特异性。这种特异性与靶DNA的结构特征相关:可弯曲性、亲A性或蛋白质诱导的可变形性。其余的LTR-逆转座子(科皮亚族和BEL族、吉普赛族的布拉斯托皮亚和412亚组)没有表现出整合特异性。布拉斯托皮亚和412亚组LTR-逆转座子的整合酶结构中存在色域,可能有助于非特异性整合过程。