9k6i
Structure of full-length human LINE-1 ORF2p with endogenous DNA and RNA/cDNA hybrid
Structural highlights
FunctionLORF2_HUMAN Has a reverse transcriptase activity required for target-primed reverse transcription of the LINE-1 element mRNA, a crucial step in LINE-1 retrotransposition. Has also an endonuclease activity that allows the introduction of nicks in the chromosomal target DNA. Cleaves DNA in AT-rich regions between a 5' stretch of purines and a 3' stretch of pyrimidines, corresponding to sites of LINE-1 integration in the genome.[1] [2] [3] Publication Abstract from PubMedLong 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. Mechanism of DNA targeting by human LINE-1.,Jin W, Yu C, Zhang Y, Cao C, Xia T, Song G, Cai Z, Xue Y, Zhu B, Xu RM Science. 2025 Oct 9;390(6769):eadu3433. doi: 10.1126/science.adu3433. Epub 2025 , Oct 9. PMID:41066570[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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