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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Triplex-forming oligophosphoramidates containing thymines and cytosines or 5-methyl cytosines (5' T4CT4C6T 3') bind strongly to a 16 basepair oligopurine.oligopyrimidine sequence of HIV proviral DNA even at neutral pH. These triple-helical complexes formed with oligonucleotide analogues with N3'-->P5' phosphoramidate linkages are remarkably stable compared to oligonucleotides with natural phosphodiester linkages. In transcription assays the (T,C)-containing phosphoramidate oligomers induce an efficient arrest of both bacteriophage and eukaryotic transcriptional machineries under conditions where the isosequential phosphodiesters have no inhibitory effect. In both cases the RNA polymerase (SP6, T7 or Pol II) is physically blocked by the non-covalent triplex and RNA synthesis is stopped at the triplex site. However the eukaryotic transcription machinery is blocked more efficiently (at submicromolar concentration) than the bacteriophage polymerases. The analysis of the 3'-ends of the truncated transcripts provides evidence for differences in the termination patterns induced by the triplex barrier for the bacteriophage and the eukaryotic systems. This in vitro comparative study provides the basis for the rational design of strong transcriptional inhibitors. The efficient in vitro inhibition obtained using the phosphoramidate oligomers in the eukaryotic transcription assay makes them good candidates for the development of sequence-specific antigene agents.
J Mol Biol 1996 Aug 23
PMID:Efficient inhibition of transcription elongation in vitro by oligonucleotide phosphoramidates targeted to proviral HIV DNA. 878 Jul 81

The organization of eukaryotic chromosomes into topological domains has led to the assumption that DNA topology and perhaps supercoiling are involved in eukaryotic nuclear processes. Xenopus oocytes provide a model system for studying the role of DNA topology in transcription. Linear plasmid templates for RNA polymerases (Pols) I and II are not transcribed in Xenopus oocytes, while circular templates are transcriptionally active. Here we show that circularity is not required for transcription of Pol I or Pol II promoters if the linear template is sufficiently long (> 17 to 19 kb). The Xenopus rRNA (Pol I) promoter is active in central positions on a long linear template but is not transcribed when located near an end. Because supercoils generated by transcription could be retained by viscous drag against the long template, these results are consistent with a supercoiling requirement for this promoter. Surprisingly, the herpes simplex virus thymidine kinase (Pol II) promoter is active even 100 bp from the end of the long template, indicating that template length fulfills a critical parameter for transcription that is not consistent with a supercoiling requirement. These results show that DNA length has unrecognized importance for transcription in vivo.
Mol Cell Biol 1996 Oct
PMID:DNA length is a critical parameter for eukaryotic transcription in vivo. 881 96

Antisera raised against proliferating cell nuclear antigen (PfPCNA) and DNA polymerase delta (PfDNA Pol delta) have been used against extracts from synchronised parasites to show that both proteins accumulate in trophozoites and persist in schizonts. The steady-state transcripts from both PfPCNA and PfDNA Pol delta also accumulate at the trophozoite stage. However, nuclear run on analysis shows that, whereas PfDNA Pol delta promoter activity is absent in rings but present in trophozoites and schizonts, the PfPCNA promoter is active throughout the intraerythrocytic cycle. This suggests that mechanisms regulating the expression of these two genes may be different although their coordinated activity is required for DNA replication.
Mol Biochem Parasitol 1996 Aug
PMID:Stage specific expression of proliferating cell nuclear antigen and DNA polymerase delta from Plasmodium falciparum. 885 54

Efficient transcription elongation by RNA polymerase I (Pol I) requires a specific Pol I-associated factor, termed TIF-IC. Here we show that TFIIS, a factor that has previously been shown to promote read-through past many types of blocks to elongation by RNA polymerase II, also enhances Pol I-directed transcription elongation. In a reconstituted transcription system containing purified proteins, TFIIS stimulates Pol I transcription by increasing the overall rate of RNA chain elongation. As with Pol II, ternary Pol I complexes cleave the 3' end of the nascent transcripts in response to TFIIS. The truncated RNAs remain bound to the template, are subject to pyrophosphorolysis, and can be chased into longer transcripts. Moreover, we show by immunoprecipitation and specific affinity chromatography that TFIIS physically interacts with Pol I. The results suggest that nascent transcript cleavage by TFIIS or a TFIIS-related factor may be a general mechanism by which both Pol I and Pol II can bypass transcriptional impediments.
Mol Gen Genet 1996 Sep 25
PMID:TFIIS binds to mouse RNA polymerase I and stimulates transcript elongation and hydrolytic cleavage of nascent rRNA. 887 42

We report the cloning of RRN11, a gene coding for a 66-kDa protein essential for transcription initiation by RNA polymerase I (Pol I) in the yeast Saccharomyces cerevisiae. Rrn11 specifically complexes with two previously identified transcription factors, Rrn6 and Rrn7 (D. A. Keys, J. S. Steffan, J. A. Dodd, R. T. Yamamoto, Y. Nogi, and M. Nomura, Genes Dev. 8:2349-2362, 1994). The Rrn11-Rrn6-Rrn7 complex also binds the TATA-binding protein and is required for transcription by the core domain of the Pol I promoter. Therefore, we have designated the Rrn11-Rrn6-Rrn7-TATA-binding protein complex the yeast Pol I core factor. A two-hybrid assay was used to demonstrate involvement of short leucine heptad repeats on both Rrn11 and Rrn6 in the in vivo association of these two proteins. This assay also verified the previously described strong association between Rrn6 and Rrn7, independent of the Rrn6 leucine repeat.
Mol Cell Biol 1996 Nov
PMID:A novel 66-kilodalton protein complexes with Rrn6, Rrn7, and TATA-binding protein to promote polymerase I transcription initiation in Saccharomyces cerevisiae. 888 72

Genetic and biochemical studies of Saccharomyces cerevisiae have indicated the involvement of a large number of protein factors in nucleotide excision repair (NER) of UV-damaged DNA. However, how MMS19 affects this process has remained unclear. Here, we report on the isolation of the MMS19 gene and the determination of its role in NER and other cellular processes. Genetic and biochemical evidence indicates that besides its function in NER, MMS19 also affects RNA polymerase II (Pol II) transcription. mms19delta cells do not grow at 37 degrees C, and mutant extract exhibits a thermolabile defect in Pol II transcription. Thus, Mms19 protein resembles TFIIH in that it is required for both transcription and DNA repair. However, addition of purified Mms19 protein does not alleviate the transcriptional defect of the mms19delta extract, nor does it stimulate the incision of UV-damaged DNA reconstituted from purified proteins. Interestingly, addition of purified TFIIH corrects the transcriptional defect of the mms19delta extract. Mms19 is, however, not a component of TFIIH or of Pol II holoenzyme. These and other results suggest that Mms19 affects NER and transcription by influencing the activity of TFIIH as an upstream regulatory element. It is proposed that mutations in the human MMS19 counterpart could result in syndromes in which both NER and transcription are affected.
Mol Cell Biol 1996 Dec
PMID:Dual requirement for the yeast MMS19 gene in DNA repair and RNA polymerase II transcription. 894 33

The African trypanosome Trypanosoma brucei is a protozoan parasite that causes the disease African sleeping sickness. The parasite avoids the host's immune response by the process of antigenic variation, or by sequentially expressing antigenically different cell-surface coat proteins. These proteins, called variant surface glycoproteins (VSGs), are expressed from a specific locus, the VSG gene expression site (ES). In an attempt to understand expression of VSG genes, we expanded on earlier investigations of the promoter that controls the large VSG gene expression site transcription unit. We studied VSG ES promoter function both in transient transfection assays, and after stable integration at a chromosomal locus. Analysis of closely spaced deletion mutants showed that the minimum VSG ES promoter fragment that gives full activity is extremely small, and mapped precisely to a fragment that contains no more than -67 bp 5' to the putative transcription initiation site. The promoter lacked an upstream control element, or UCE, an element found at the PARP promoter, and at most eukaryotic Pol I promoters. Furthermore, linker scanning mutagenesis demonstrated that the VSG ES promoter contains at least two essential regulatory elements, including sequences within the region -67/-60 and the region -35/-20, both numbered relative to the initiation site. An altered promoter with mutated nucleotides surrounding the transcription initiation site still directed wild-type levels of expression. In this study, the results were similar for both insect and bloodstream form trypanosomes, suggesting that the same basic machinery for expression from the VSG ES promoter is found in both stages of the parasite.
Mol Biochem Parasitol 1996 Jan
PMID:A detailed mutational analysis of the VSG gene expression site promoter. 899 22

Replication of plasmid pAM beta 1 is initiated by DNA polymerase I (Pol I) and completed by DNA polymerase III holoenzyme contained in the replisome machinery. In this study we report that initiation of DNA replication generates D-loop structures containing the nascent leading strand paired to its template, and that D-loop extension is arrested approximately 230 bp from the initiation site of DNA synthesis in the presence of the plasmid-encoded resolvase. In vitro and in vivo data suggest that this arrest is caused by a collision between Pol I and the resolvase bound to its target. As the arrested D-loop replication intermediates carry a single-stranded primosome-assembly site, we hypothesize that the biological role of the replication arrest is to limit the region replicated by Pol I and to promote the replacement of Pol I by the replisome in order to initiate concerted synthesis of the leading and lagging strands.
Mol Microbiol 1997 Feb
PMID:Replication terminus for DNA polymerase I during initiation of pAM beta 1 replication: role of the plasmid-encoded resolution system. 904 86

Our group demonstrated recently that the 3' ends of several families of tRNA-derived SINEs (short interspersed repetitive elements) originated from the 3' ends of LINEs (long interspersed repetitive elements) [Ohshima et al. (1996) Mol. Cell. Biol. 16:3756-3764]. Two fully characterized examples of such organization were provided by the tortoise Pol III/SINE and the salmonid HpaI family of SINEs, and two probable examples were provided by the tobacco TS family of SINEs and the salmon SmaI family of SINEs. This organization of SINEs can explain their potential to retropose in the genome since it appears reasonable that the sites for recognition of LINEs by reverse transcriptase should be located within the 3'-end sequences of LINEs. We now add another example to this category of SINEs. In the bovine genome, there are Bov-tA SINEs, which belong to the superfamily of tRNA-derived families of SINEs, and Bov-B LINEs, which were recently demonstrated to belong to a LINE family. Moreover, Bov-tA and Bov-B share the same 3'-end tail. We propose a possible scenario whereby the composite structure of the bovine Bov-tA family of SINEs might have been generated from the Bov-B family of LINEs during evolution.
J Mol Evol 1997
PMID:The 3' ends of tRNA-derived SINEs originated from the 3' ends of LINEs: a new example from the bovine genome. 907 Oct 12

A34.5, a phosphoprotein copurifying with RNA polymerase I (Pol I), lacks homology to any component of the Pol II or Pol III transcription complexes. Cells devoid of A34.5 hardly affect growth and rRNA synthesis and generate a catalytically active but structurally modified enzyme also lacking subunit A49 upon in vitro purification. Other Pol I-specific subunits (A49, A14, and A12.2) are nonessential for growth at 30 degrees C but are essential (A49 and A12.2) or helpful (A14) at 25 or 37 degrees C. Triple mutants without A34.5, A49, and A12.2 are viable, but inactivating any of these subunits together with A14 is lethal. Lethality is rescued by expressing pre-rRNA from a Pol II-specific promoter, demonstrating that these subunits are collectively essential but individually dispensable for rRNA synthesis. A14 and A34.5 single deletions affect the subunit composition of the purified enzyme in pleiotropic but nonoverlapping ways which, if accumulated in the double mutants, provide a structural explanation for their strict synthetic lethality. A34.5 (but not A14) becomes quasi-essential in strains lacking DNA topoisomerase I, suggesting a specific role of this subunit in helping Pol I to overcome the topological constraints imposed on ribosomal DNA by transcription.
Mol Cell Biol 1997 Apr
PMID:A34.5, a nonessential component of yeast RNA polymerase I, cooperates with subunit A14 and DNA topoisomerase I to produce a functional rRNA synthesis machine. 912 26


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