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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Initiation of Adenovirus DNA replication in vitro requires the presence of three viral proteins (pTP, pol, DBP) and two cellular transcription factors, NFI and Oct-1, that stimulate replication more than 100-fold. NFI assists in binding and positioning of the DNA polymerase in the origin whereas Oct-1 changes the structure of origin DNA. Optimal templates contain, in addition to origin sequences, the covalently bound viral terminal protein (TP). This terminal protein stimulates the template activity over 20 fold compared to protein-free templates. To study the way in which TP exerts its function in vitro we devised a novel method to isolate and label a short origin containing fragment in which the TP was bound in a functional form. This fragment replicated very efficiently and could be used for studying the binding of other replication proteins. Employing alpha-chymotrypsin digestion we show that for enhancement of replication in vitro only a small part of TP is required.
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PMID:Adenovirus DNA replication: the function of the covalently bound terminal protein. 129 Dec 41

The Adenovirus DNA-binding protein (DBP) binds to single-stranded (ss) DNA as well as to double-stranded (ds) DNA and forms multimeric protein-DNA complexes with both. Gel retardation assays indicate rapid complex formation for both DNAs. DBP rapidly dissociates from dsDNA, indicating a dynamic equilibrium, whereas the ssDNA-DBP complex is much more stable. We investigated the complex between DBP and dsDNA in more detail. Electron microscopical analysis shows thick filament-like and beaded structures in which the length of the DNA is not significantly altered. Cryo-electron micrographs suggest the presence of interwound protein fibres around the DNA. Ligase-mediated cyclization, but not linear multimerization, of DBP-saturated DNA fragments exceeding the persistence length was severely inhibited. This suggests that DNA may be organized by DBP into a rigid structure. Under those conditions, DBP induces distinct changes in the circular dichroism spectrum of the DNA, indicative of structural DNA changes. No bending or twisting of the complex was observed. Hydroxyl radical footprinting showed that the breakdown pattern of DNA at saturating DBP concentrations is much more regular than the protein-free DNA. This suggests the removal of tertiary structures, which may be related to the effects of DBP on enhanced NFI binding and chain elongation during Adenovirus DNA replication. Using purified proteins in an in vitro replication system, we correlate the structural changes with the effects of DBP on enhancement of NFI-binding as well as on DNA replication.
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PMID:Structural alterations of double-stranded DNA in complex with the adenovirus DNA-binding protein. Implications for its function in DNA replication. 131 98

POU domain proteins constitute a family of eukaryotic transcription factors that exert critical functions during development. They contain a conserved 160 amino acids DNA binding domain, the POU domain. Genetic data have demonstrated that some POU domain proteins are essential for the proliferation of specific cell types, suggesting a possible role in DNA replication. In addition, the ubiquitous POU transcription factor Oct-1 or its isolated POU domain enhances adenovirus DNA replication. Here we compared the DNA binding specificities of POU domain proteins from different subclasses. They exhibit overlapping, yet distinct binding site preferences. Furthermore, purified Pit-1, Oct-1, Oct-2, Oct-6, Oct-4 and zebrafish POU[C] could all stimulate adenovirus DNA replication in a reconstituted in vitro system. Thus, activation appears to depend on a property common to most POU domain proteins. Adenovirus DNA replication is also stimulated by the transcription factor NFI/CTF. In contrast to NFI, the POU domain did not enhance binding of precursor terminal protein-DNA polymerase to the origin nor did it stabilize the preinitiation complex. These results suggest that the POU domain acts on a rate limiting step after formation of the preinitiation complex.
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PMID:POU domain transcription factors from different subclasses stimulate adenovirus DNA replication. 147 98

Chicken TGGCA proteins belong to the ubiquitous, eukaryotic family of NFI-like nuclear proteins, which share an identical DNA binding specificity. They are involved in viral and cellular aspects of transcriptional regulation and they are capable of stimulating Adenovirus initiation of replication. Using microsequencing data from peptides of isolated proteins and PCR supported cloning, we have derived four cDNAs for NFI/TGGCA proteins, which are encoded by three separate chicken genes. Sequence alignments of NFI proteins from chicken and various mammalian species provide evidence for a common genetic equipment among higher eukaryotes, in which several related genes, employing each differential RNA splicing generate an unexpectedly large family of diverse NFI proteins. The extensive similarity of the amino acid sequence throughout the complete coding regions between products of the same gene type in different species indicates a uniform selection pressure on all protein parts, also on those outside the DNA-binding domain.
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PMID:Chicken NFI/TGGCA proteins are encoded by at least three independent genes: NFI-A, NFI-B and NFI-C with homologues in mammalian genomes. 233 52

Adenovirus DNA binding protein is a multifunctional protein essential for viral DNA replication. To investigate the role of the DNA binding protein in this process its interaction with partial DNA duplexes was examined. Duplex regions of DNA, created when a short DNA strand is annealed to its complementary sequence present in the single stranded form of M13 phage DNA, were efficiently unwound by DNA binding protein in a reaction that required neither ATP nor MgCl2. The unwinding activity of DNA binding protein was reduced by conditions which increased the stability of DNA duplexes. DNA unwinding by DNA binding protein was highly co-operative and required the single stranded DNA to be completely coated with the protein. Completely double stranded DNA could also be unwound by DNA binding protein but this reaction was sensitive to the G+C content of the DNA and could only be observed with relatively short DNA duplexes up to 45 base pairs in length. When these short double stranded DNA molecules contained binding sites for the transcription factors NFI and NFIII addition of the cognate factor blocked DNA binding protein mediated unwinding of the particular DNA duplex. Cleavage of DNA binding protein with chymotrypsin and isolation of the 39,000 molecular weight C-terminal fragment indicated that the unwinding activity was located in this domain of the protein. In support of this contention a monoclonal antibody, which had previously been mapped to this region, specifically inhibited the DNA unwinding activity. These activities of DNA binding protein are likely to be involved in DNA replication, where the destabilisation of DNA duplexes could be important both during initiation and elongation.
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PMID:Adenovirus DNA binding protein: helix destabilising properties. 813 13