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TitleMechanism of DNA targeting by human LINE-1.
Journal, issue, pagesScience, Vol. 390, Issue 6769, Page eadu3433, Year 2025
Publish dateOct 9, 2025
AuthorsWenxing Jin / Cong Yu / Yan Zhang / Changchang Cao / Tianfan Xia / Ge Song / Zhaokui Cai / Yuanchao Xue / Bing Zhu / Rui-Ming Xu /
PubMed AbstractLong 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 ...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.
External linksScience / PubMed:41066570
MethodsEM (single particle)
Resolution3.0 - 3.6 Å
Structure data

62126

9k6g

EMDB-62126, PDB-9k6g:
Structure of human LINE-1 ORF2p with endogenous dsDNA and RNA/cDNA hybrid
Method: EM (single particle) / Resolution: 3.3 Å

62127

9k6h

EMDB-62127, PDB-9k6h:
Structure of human LINE-1 ORF2p with endogenous DNA and RNA/cDNA hybrid bound to dNTP and Mn2+
Method: EM (single particle) / Resolution: 3.0 Å

62128

9k6i

EMDB-62128, PDB-9k6i:
Structure of full-length human LINE-1 ORF2p with endogenous DNA and RNA/cDNA hybrid
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-DTP:
2'-DEOXYADENOSINE 5'-TRIPHOSPHATE

ChemComp-MN:
Unknown entry

Source
  • homo sapiens (human)
  • trichoplusia ni (cabbage looper)
KeywordsGENE REGULATION / Endonuclease / Reverse transcriptase

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