LINE retrotransposition and host DNA repair machinery.

Mobile genetic elements Pub Date : 2015-10-20 eCollection Date: 2015-11-01 DOI:10.1080/2159256X.2015.1096998
Katsumi Yamaguchi, Masaki Kajikawa, Norihiro Okada
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Abstract

Long interspersed elements (LINEs), or non-long-terminal repeat (LTR) retrotransposons, are mobile genetic elements that exist in the genomic DNA of most eukaryotes, comprising a considerable portion of the host chromosomes. LINEs constitute endogenous mutagens that cause insertional mutations in host chromosomes and have a large impact on host genome evolution. Despite their importance, however, the molecular mechanism of LINE retrotransposition is not fully understood. Several studies suggest that host proteins that participate in the repair of DNA breaks modulate LINE retrotransposition. Recently, we provided evidence that there are 2 distinct pathways-annealing and direct-that join the 5'-end of LINEs to host chromosomal DNA. These pathways appear to be used distinctively by zebrafish LINEs and the human L1 in DT40 cells. In HeLa cells, only the annealing pathway appears to be used. This implies that different characteristics of the 2 LINEs and also host factors dictate which pathway is selected. Here, we discuss the 5'-end-joining pathways of LINE retrotransposition and propose that the pathways of LINE integration adopt certain host repair factors.

Abstract Image

Abstract Image

LINE逆转录和宿主DNA修复机制
长穿插元件(LINEs)或非长端重复(LTR)反转座子是存在于大多数真核生物基因组 DNA 中的移动遗传元件,占宿主染色体的很大一部分。LINEs 是内源性突变因子,可导致宿主染色体发生插入突变,对宿主基因组的进化产生巨大影响。尽管LINE非常重要,但其逆转录的分子机制尚未完全清楚。一些研究表明,参与DNA断裂修复的宿主蛋白质会调节LINE逆转录。最近,我们提供的证据表明,有两种不同的途径--退火和直接--将 LINE 的 5'-end 连接到宿主染色体 DNA 上。在 DT40 细胞中,斑马鱼 LINE 和人类 L1 似乎分别使用这两种途径。在HeLa细胞中,似乎只使用退火途径。这意味着两种LINEs的不同特性以及宿主因素决定了选择哪种途径。在此,我们讨论了LINE逆转录的5'-末端连接途径,并提出LINE整合途径采用了某些宿主修复因子。
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