Mechanism of DNA targeting by human LINE-1

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-10-09 DOI:10.1126/science.adu3433

Wenxing Jin, Cong Yu, Yan Zhang, Changchang Cao, Tianfan Xia, Ge Song, Zhaokui Cai, Yuanchao Xue, Bing Zhu, Rui-Ming Xu

引用次数: 0

Abstract

Long interspersed nuclear element–1 (LINE-1 or L1), the only autonomously active retrotransposon in humans today, constitutes a large proportion of the genome and continues to evolve the genome and impact fundamental biological processes. L1 retrotransposition critically depends on its endonuclease and reverse transcriptase subunit open reading frame 2 protein (ORF2p), which targets genomic loci and nicks DNA using an evolutionarily distinct yet not fully understood mechanism. Our structural and biochemical analyses revealed that ORF2p is a structure-dependent endonuclease. It binds a double-stranded DNA region upstream of the nicking site and recognizes a downstream forked or flap structure for efficient DNA nicking. This discovery suggests that L1 mobilization piggybacks on chromosomal processes with noncanonical DNA structure intermediates.

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人LINE-1的DNA靶向机制

长散布核元件-1 （LINE-1或L1）是当今人类中唯一自主活性的反转录转座子，构成了基因组的很大一部分，并继续进化基因组并影响基本的生物过程。L1逆转录转位主要依赖于其内切酶和逆转录酶亚基开放阅读框2蛋白（ORF2p），其靶向基因组位点并使用一种进化上不同但尚未完全了解的机制来切割DNA。我们的结构和生化分析表明ORF2p是一种结构依赖的内切酶。它与缺口位点上游的双链DNA区域结合，并识别下游的分叉或皮瓣结构，以实现有效的DNA缺口。这一发现表明，L1的动员依赖于非规范DNA结构中间体的染色体过程。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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