Targeting of human retrotransposon integration is directed by the specificity of the L1 endonuclease for regions of unusual DNA structure

Gregory J. Cost, Jef D. Boeke

Research output: Contribution to journalArticle

Abstract

L1 elements are polyA retrotransposons which inhabit the human genome. Recent work has defined an endonuclease (L1 EN) encoded by the L1 element required for retrotransposition. We report the sequence specificity of this nicking endonuclease and the physical basis of its DNA recognition. L1 endonuclease is specific for the unusual DNA structural features found at the TpA junction of 5'(dT(n)-dA(n))·5'(dT(n)-dA(n)) tracts. Within the context of this sequence, substitutions which generate a pyrimidine-purine junction are tolerated, whereas purine-pyrimidine junctions greatly reduce or eliminate nicking activity. The A-tract conformation of the DNA substrate 5' of the nicked site is required for L1 EN nicking. Chemical or physical unwinding of the DNA helix enhances L1 endonuclease activity, while disruption of the adenine mobility associated with TpA junctions reduces it. Akin to the protein-DNA interactions of DNase I, L1 endonuclease DNA recognition is likely mediated by minor groove interactions. Unlike several of its homologues, however, L1 EN exhibits no AP endonuclease activity. Finally, we speculate on the implications of the specificity of the L1 endonuclease for the parasitic relationship between retroelements and the human genome.

Original languageEnglish (US)
Pages (from-to)18081-18093
Number of pages13
JournalBiochemistry®
Volume37
Issue number51
DOIs
StatePublished - Dec 22 1998

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Retroelements
Endonucleases
Long Interspersed Nucleotide Elements
DNA
Deoxyribonuclease I
Human Genome
Genes
DNA-(Apurinic or Apyrimidinic Site) Lyase
Nucleic Acid Conformation
Adenine
Conformations
Substitution reactions
Substrates
Proteins

ASJC Scopus subject areas

  • Biochemistry

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Targeting of human retrotransposon integration is directed by the specificity of the L1 endonuclease for regions of unusual DNA structure. / Cost, Gregory J.; Boeke, Jef D.

In: Biochemistry®, Vol. 37, No. 51, 22.12.1998, p. 18081-18093.

Research output: Contribution to journalArticle

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