Targeting of DNA polymerase to the adenovirus origin of DNA replication by interaction with nuclear factor I

Marie Thérèse Armentero, Marshall Horwitz, Nicolas Mermod

Research output: Contribution to journalArticlepeer-review

Abstract

Efficient initiation by the DNA polymerase of adenovirus type 2 requires nuclear factor I (NFI), a cellular sequence-specific transcription factor. Three functions of NFI-dimerization, DNA binding, and activation of DNA replication-are colocalized within the N-terminal portion of the protein. To define more precisely the role of NFI in viral DNA replication, a series of site-directed mutations within the N-terminal domain have been generated, thus allowing the separation of all three functions contained within this region. Impairment of the dimerization function prevents sequence-specific DNA binding and in turn abolishes the NFI-mediated activation of DNA replication. NFI DNA-binding activity, although necessary, is not sufficient to activate the initiation of adenovirus replication. A distinct class of NFI mutations that abolish the recruitment of the viral DNA polymerase to the origin also prevent the activation of replication. Thus, a direct interaction of NFI with the viral DNA polymerase complex is required to form a stable and active preinitiation complex on the origin and is responsible for the activation of replication by NFI.

Original languageEnglish
Pages (from-to)11537-11541
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number24
DOIs
Publication statusPublished - Nov 22 1994

Keywords

  • CAAT box-binding transcription factors
  • protein-protein interaction

ASJC Scopus subject areas

  • Genetics
  • General

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