Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Mediator complex is an essential co-activator for RNA polymerase II-dependent transcription in the budding yeast Saccharomyces cerevisiae. The S. cerevisiae core Mediator complex consists of three larger domains that are termed head, middle, and tail. The Med17 subunit is located within the head domain and is essential for cell viability. A temperature-sensitive allele of the MED17 gene known as srb4-138 causes all RNA polymerase II-dependent transcription to cease at the non-permissive temperature. The phenotype of srb4-138 allele has served as the main in vivo proof of the importance of Mediator, but the molecular basis for the effect of this mutant has not been determined. We here characterize Mediator from cells carrying the srb4-138 allele and find that the Mediator complex consistently breaks apart at the head/middle domain boundary even at lower temperatures. We find that both the head and middle domains are able to associate with the RNA polymerase independently of each other. Interestingly, both sub-complexes are able to associate with an active promoter at the permissive temperature but at the non-permissive temperature the head domain is lost from the promoter.
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PMID:The classical srb4-138 mutant allele causes dissociation of yeast Mediator. 1696 61

In eukaryotes, holo-Mediator consists of four modules: head, middle, tail, and CDK/Cyclin. The head module performs an essential function involved in regulation of RNA polymerase II (Pol II). We studied the human head module subunit MED17 (hMED17). Recent structural studies showed that yeast MED17 may function as a hinge connecting the neck and movable jaw regions of the head module to the fixed jaw region. Luciferase assays in hMED17-knockdown cells showed that hMED17 supports transcriptional activation, and pulldown assays showed that hMED17 interacted with Pol II and the general transcription factors TFIIB, TBP, TFIIE, and TFIIH. In addition, hMED17 bound to a DNA helicase subunit of TFIIH, XPB, which is essential for both transcription and nucleotide excision repair (NER). Because hMED17 associates with p53 upon UV-C irradiation, we treated human MCF-7 cells with either UV-C or the MDM2 inhibitor Nutlin-3. Both treatments resulted in accumulation of p53 in the nucleus, but hMED17 remained concentrated in the nucleus in response to UV-C. hMED17 colocalized with the NER factors XPB and XPG following UV-C irradiation, and XPG and XPB bound to hMED17 in vitro. These findings suggest that hMED17 may play essential roles in switching between transcription and NER.
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PMID:Human mediator MED17 subunit plays essential roles in gene regulation by associating with the transcription and DNA repair machineries. 2548 73