Characterization of a preferred site on human chromosome 19q for integration of adeno-associated virus DNA by non-homologous recombination

EMBO J. 1992 Dec;11(13):5071-8.

Abstract

The human parvovirus, adeno-associated virus (AAV), has been shown to integrate preferentially into human chromosome 19 q13.3-qter. The human target sequence for AAV integration (AAVS1) was cloned and sequenced. By analysis of the proviral junctions it was determined that integration of the AAV DNA occurred via a non-homologous recombination pathway although there were either four or five identical nucleotides at the junctions. Integration was a multistep, concerted process that resulted in cellular sequence rearrangements. The sequence of the integration locus was analyzed for possible recombination signals. Direct repeats at a much greater than random occurrence were found distributed non-uniformly throughout the AAVS1 sequence. A CpG island containing transcription factor binding site elements is suggestive of a TATA-less promoter. Evidence for transcriptional activity was provided by PCR amplification of reverse transcribed RNA.

Publication types

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

MeSH terms

  • Base Sequence
  • Chromosomes, Human, Pair 19*
  • Cloning, Molecular
  • DNA
  • DNA, Viral / metabolism*
  • Dependovirus / physiology*
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Recombination, Genetic*
  • TATA Box
  • Transcription, Genetic
  • Virus Integration*

Substances

  • DNA, Viral
  • DNA

Associated data

  • GENBANK/D13199
  • GENBANK/D13200
  • GENBANK/D13201
  • GENBANK/D13202
  • GENBANK/D13203
  • GENBANK/M94783
  • GENBANK/M94784
  • GENBANK/M94785
  • GENBANK/S51329
  • GENBANK/X68109