人类LINE-1的DNA靶向机制，这一成果由中国科学院生物物理研究所许瑞明研究组经过不懈努力而取得。该研究于2025年10月9日发表于国际一流学术期刊《科学》杂志上。

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），其靶向基因组位点和片段DNA，这是一种进化上独特但尚未完全理解的机制。他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。

附：英文原文

Title: Mechanism of DNA targeting by human LINE-1

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

Issue&Volume: 2025-10-09

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.

DOI: adu3433

Source: https://www.science.org/doi/10.1126/science.adu3433