Open AccessTargeting of DNA polymerase to the adenovirus origin of DNA replication by interaction with nuclear factor I.
Author(s) -
Marie Thérèse Armentero,
Marshall S. Horwitz,
Nicolas Mermod
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.24.11537
Subject(s) - biology , dna replication , dna polymerase ii , replication factor c , dna polymerase , dna clamp , microbiology and biotechnology , control of chromosome duplication , origin recognition complex , replication protein a , eukaryotic dna replication , dna polymerase delta , dna polymerase i , dna replication factor cdt1 , polymerase , dna , genetics , dna binding protein , transcription factor , reverse transcriptase , gene , polymerase chain reaction
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.