Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Epstein-Barr virus (EBV) DNA polymerase (pol) is essential for the replication of viral genomes during productive EBV infection. We have previously reported that the EBV DNA pol promoter, which is TATA-less and constitutively inactive, is activated by a genomic clone expressing both immediate-early viral transactivators, BZLF1Z and BRLF1 (R), in EBV-infected lymphoid cells. Here we demonstrate that R alone is sufficient to activate the pol promoter in EBV-negative B cells. Unlike other early promoters to which the R protein binds directly, its effect on the pol promoter does not appear to involve a direct DNA-binding mechanism. Instead, we found that two cellular transcription factors, an upstream stimulatory factor USF, and a member of the E2F family of proteins, bind directly to the pol promoter at positions -795 to -786 and -186 to -170, respectively, regions previously identified as important for activation of the pol promoter. These two sites contribute to or are essential for transactivation of the pol promoter by R in EBV-noninfected B cells. These data suggest that the R immediate-early protein may activate a key early EBV promoter (pol) through both USF and E2F.
 ...
PMID:Activation of the Epstein-Barr virus DNA polymerase promoter by the BRLF1 immediate-early protein is mediated through USF and E2F. 864 84

We have isolated the genomic DNA fragment spanning the 5-end and the first four exons encoding the 68 kDa subunit (p68) of the mouse DNA polymerase alpha-primase complex [corrected]. The p68 promoter region lacks TATA and CAAT boxes, but contains a GC-rich sequence, two palindrome sequences and two putative E2F-binding sites [corrected]. A series of transient expression assays using a luciferase reporter gene indicated that a region from nucleotide position -89 to -30 (-89/-30) with respect to the transcription initiation site is crucial for basal transcription of the p68 gene in proliferating NIH 3T3 cells. In particular, part of the GC-rich sequence (-57/-46) and the palindrome (-81/-62) elements were necessary for promoter activity, both of which share homology with the E-box sequence. Gel mobility shift assays using NIH 3T3 nuclear extracts revealed that the upstream stimulatory factor, known as an E-box-binding protein, binds to these sites. Moreover, we observed binding of E2F to two sites near the transcription initiation site (-11/-3 and +9/+16). A transient luciferase expression assay using synchronized NIH 3T3 cells in G(0)phase revealed that these E2F sites are essential for transcription induction of the p68 gene after serum stimulation, but are dispensable for basal transcription. These results indicate that growth-dependent regulation of transcription of the mouse p68 and p180 genes is mediated by a common factor, E2F; however, basal transcription of the genes, interestingly, is regulated by different transcription factors.
 ...
PMID:Cloning and characterization of the 5'-upstream sequence governing the cell cycle-dependent transcription of mouse DNA polymerase alpha 68 kDa subunit gene. 1071 Apr 18

Simian varicella virus (SVV) is a neurotropic alphaherpesvirus that causes a natural, varicella-like disease in non-human primates. After resolution of the primary disease, SVV, like its human counterpart, varicella-zoster virus (VZV), establishes latent infection in the neural ganglia of the host. In this study, gene expression of SVV open reading frames (ORFs) 28 and 29, which encode the viral DNA polymerase and DNA-binding protein, respectively, was characterized during lytic infection of Vero cells. The results indicate that the intergenic region controlling gene 28 and 29 expression includes overlapping, divergent promoters. The ORF 28 and 29 promoters are active in SVV-infected Vero cells, but not in uninfected cells. The SVV immediate-early gene 62 (IE62) product transactivates ORF 28 and 29 expression, and a cellular upstream stimulatory factor-binding site is important for efficient IE62 induction of genes 28 and 29. DNA sequence analysis of the 185 bp intergenic region identified putative cellular transcription factor-binding sites. Transcriptional analysis mapped ORF 28 and 29 RNA start sites. A recombinant SVV was employed to demonstrate that the ORF 29 promoter can express a heterologous gene (green fluorescent protein) when inserted into a novel site (the ORF 12/13 intergenic region) within the SVV genome. The findings demonstrate similarities between SVV and VZV ORF 28/29 expression and indicate that the simian varicella model may be useful to investigate the differential regulation of viral genes during lytic and latent infection.
 ...
PMID:Simian varicella virus gene 28 and 29 promoters share a common upstream stimulatory factor-binding site and are induced by IE62 transactivation. 1669 Sep 14