人类LINE-1的DNA靶向机制，这一成果由188比分直播: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