Mechanism of DNA targeting by human LINE-1.
basic_science · Level V
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- Record sourced from PubMed, PMID 41066570.
- Also identified by DOI 10.1126/science.adu3433.
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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.
Medical subject headings
- DNA
- DNA Breaks, Double-Stranded
- Long Interspersed Nucleotide Elements
- Deoxyribonuclease I