Genetic evidence that the non-homologous end-joining repair pathway is involved in LINE retrotransposition.
Genetic evidence that the non-homologous end-joining repair pathway is involved in LINE retrotransposition.
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DOI：
10.1371/journal.pgen.1000461
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发表时间：
2009-04
期刊：
影响因子：
4.5
通讯作者：
Okada N
中科院分区：
文献类型：
--
作者：
Suzuki J;Yamaguchi K;Kajikawa M;Ichiyanagi K;Adachi N;Koyama H;Takeda S;Okada N
长散布元件（LINES）是在真核生物基因组内增殖的转座元件，对真核生物基因组进化有很大影响。LINES通过一个称为逆转录的过程动员。尽管LINE编码的蛋白质在逆转录转座中的作用已被广泛研究，但宿主编码的因子在逆转录转座中的参与仍不清楚。为了解决这个问题，我们研究了两种结构不同的LINEs-斑马鱼ZfL 2 -2和人L1-在基因敲除鸡DT 40细胞系中的反转录转座频率，这些细胞系缺乏参与DNA的非同源末端连接（NHEJ）修复的基因，并且在用抑制NHEJ的药物处理的人HeLa细胞中。在这些细胞中，NHEJ蛋白的缺陷降低了两种LINE的反转录转座频率，表明NHEJ参与LINE反转录转座。ZfL 2 -2在DT 40细胞中插入的更精确表征允许我们考虑NHEJ在LINE反转录转座中的双重作用的可能性，即确保LINE的有效整合并限制其全长形成。长散布元件（LINES）是在真核生物基因组中移动和扩增其自身拷贝的转座元件。尽管LINE一直被认为是“垃圾”DNA，但最近的研究表明，LINE诱导的宿主染色体改变是真核生物基因组进化的主要驱动力。LINE通过一种称为逆转录转座的机制移动，其中转录的LINE RNA逆转录成DNA，然后整合到宿主染色体中。尽管LINE编码的蛋白质在逆转录转座中的作用已被揭示，但宿主编码的蛋白质的参与尚未得到很好的研究。在这里，使用敲除鸡DT 40细胞系，我们提出的遗传证据表明，宿主编码的蛋白质参与修复DNA双链断裂参与LINE反转录转座。在DT 40细胞中LINE插入的更精确表征表明这些宿主DNA修复蛋白在LINE逆转录转座中具有双重作用;一种功能是LINE有效整合所需的，另一种功能限制了它们的全长形成。
Long interspersed elements (LINEs) are transposable elements that proliferate within eukaryotic genomes, having a large impact on eukaryotic genome evolution. LINEs mobilize via a process called retrotransposition. Although the role of the LINE-encoded protein(s) in retrotransposition has been extensively investigated, the participation of host-encoded factors in retrotransposition remains unclear. To address this issue, we examined retrotransposition frequencies of two structurally different LINEs—zebrafish ZfL2-2 and human L1—in knockout chicken DT40 cell lines deficient in genes involved in the non-homologous end-joining (NHEJ) repair of DNA and in human HeLa cells treated with a drug that inhibits NHEJ. Deficiencies of NHEJ proteins decreased retrotransposition frequencies of both LINEs in these cells, suggesting that NHEJ is involved in LINE retrotransposition. More precise characterization of ZfL2-2 insertions in DT40 cells permitted us to consider the possibility of dual roles for NHEJ in LINE retrotransposition, namely to ensure efficient integration of LINEs and to restrict their full-length formation. Long interspersed elements (LINEs) are transposable elements that mobilize and amplify their own copies within eukaryotic genomes. Although LINEs had been considered as “junk” DNA, recent studies have suggested that the LINE-induced alterations of host chromosomes are a major driving force for eukaryotic genome evolution. LINEs mobilize via a mechanism called retrotransposition, in which transcribed LINE RNA is reverse transcribed into DNA that is then integrated into the host chromosome. Although the role of LINE-encoded proteins in retrotransposition has been revealed, the participation of host-encoded proteins has not been well investigated. Here, using knockout chicken DT40 cell lines, we present genetic evidence that the host-encoded proteins involved in repair of DNA double-strand breaks participate in LINE retrotransposition. More precise characterization of LINE insertions in DT40 cells suggested dual roles for these host DNA repair proteins in LINE retrotransposition; one function is required for efficient integration of LINEs and the other restricts their full-length formation.
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