Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition

Cell. 1996 Nov 29;87(5):905-16. doi: 10.1016/s0092-8674(00)81997-2.


Human L1 elements are highly abundant poly(A) (non-LTR) retrotransposons whose second open reading frame (ORF2) encodes a reverse transcriptase (RT). We have identified an endonuclease (EN) domain at the L1 ORF2 N-terminus that is highly conserved among poly(A) retrotransposons and resembles the apurinic/apyrimidinic (AP) endonucleases. Purified L1 EN protein (L1 ENp) makes 5'-PO4, 3'-OH nicks in supercoiled plasmids, shows no preference for AP sites, and preferentially cleaves sequences resembling L1 in vivo target sequences. Mutations in conserved amino acid residues of L1 EN abolish its nicking activity and eliminate L1 retrotransposition. We propose that L1 EN cleaves the target site for L1 insertion and primes reverse transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Conserved Sequence
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • DNA, Bacterial / isolation & purification
  • DNA, Superhelical / metabolism
  • Endonucleases / genetics*
  • Endonucleases / metabolism*
  • HeLa Cells / physiology
  • Humans
  • Molecular Sequence Data
  • Mutagenesis / genetics
  • Open Reading Frames / genetics
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / ultrastructure
  • Retroelements / genetics*
  • Sequence Analysis, DNA
  • Substrate Specificity


  • DNA, Bacterial
  • DNA, Superhelical
  • RNA, Messenger
  • Retroelements
  • Endonucleases

Associated data

  • GENBANK/Z73497