Disruption of the terminal base pairs of retroviral DNA during integration

Brian P. Scottoline, Samson Chow, Viola Ellison, Patrick O. Brown

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Integrase catalyzes two essential steps in the integration of the retrovital genome-end processing and strand transfer-both of which require the interaction of integrase with vital att sites located at the ends of viral genomic DNA. These two different polynucleotidyl transfer reactions are apparently carried out by a single active site. The end product of these reactions, the integrated provirus, does not undergo transposition and remains a stable part of the host cell genome. A central question in understanding the mechanism of integration is how a single active site accomplishes two distinct polynucleotidyl transfer reactions. We propose that integrase distorts DNA substrates to accommodate both reactions within the active site. Evidence is provided for disruption of base-pairing at the terminus of vital DNA during end processing. Furthermore, we show that this end fraying is a required step in end processing and that it appears to occur after initial binding of the vital DNA end. This requirement for base-pair disruption may account for the inability of integrase to use internal sites on DNA molecules as vital att sites. The specificity of integrase for DNA ends solves a problem posed by the long terminal repeat structure of the viral genome, and may help to prevent transposition of integrated proviruses.

Original languageEnglish (US)
Pages (from-to)371-382
Number of pages12
JournalGenes and Development
Volume11
Issue number3
DOIs
StatePublished - Feb 1 1997
Externally publishedYes

Keywords

  • DNA distortion
  • Recombination
  • end processing
  • retroviral integration

ASJC Scopus subject areas

  • General Medicine

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