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 gene which specifies a subunit of RNA polymerase II, ama-1, is assigned to chromosome 7 in the Chinese hamster. The assignment of genes coding for TK, GALK, and ACP to chromosome 7 is confirmed, with a provisional regional assignment of TK and GALK to 7q. On the basis of one clone with six subclones, a provisional assignment of TPI to Chinese hamster chromosome 8 is made. With the assignment of tk and ama-1 to chromosome 7 in the CHO cell line Ama1, this chromosome is shown to have two selectable markers.
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PMID:Genetic control of drug resistance: assignment of ama-1 to Chinese hamster chromosome 7, confirmation of assignment of genes coding for TK, GALK, and ACP to chromosome 7, and tentative assignment of TPI to chromosome 8. 683 56

Human tuberculosis is still one of the most frequent causes of death worldwide. Despite the implementation of therapeutic regimes combining four drugs, the rise of resistant and multidrug-resistant Mycobacterium tuberculosis strains has compromised their efficacy. Two of the most effective anti-tubercular drugs in use, rifampicin and isoniazid, have been closely studied due to their therapeutic importance. These studies have led to the identification of the genes involved in resistance mechanisms and of those encoding the molecular targets for these drugs. Rifampicin is an inhibitor of the beta-subunit of the RNA polymerase of prokaryotes, including M. tuberculosis. Resistance to rifampicin is mediated by mutations clustered in a small region of the rpoB gene. A fraction of resistant strains showed no mutations in rpoB, suggesting that other mechanisms of resistance, possibly efflux pumps, may exist. Isoniazid is a pro-drug activated by KatG, a catalase-peroxidase. Mutations in katG, the most commonly found in M. tuberculosis clinical isolates, give high levels of resistance. In spite of this, the molecular target for isoniazid is InhA, an enoyl-ACP-reductase involved in the biosynthesis of mycolic acids. Other mutations causing resistance to isoniazid have been mapped to ndh, a gene encoding the NADH dehydrogenase.
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PMID:[Mechanisms of action of and resistance to rifampicin and isoniazid in Mycobacterium tuberculosis: new information on old friends]. 1703 59

We employed an evolutionary genomics approach to detect genes under lineage-specific positive selection for the two closely related Mycobacterium tuberculosis strains, the virulent H37Rv and the avirulent H37Ra, with the clinical isolate CDC1551 as the outgroup. We found six H37Rv-specific and six H37Ra-specific positively selected genes, among which the former comprised a flavoprotein, a RNA polymerase sigma factor SigM, two PPE family proteins, as well as two hypothetical proteins, while the latter consisted of a dehydrogenase, a (3R)-hydroxyacyl-ACP dehydratase subunit HadA, a PPE family protein, and three PE-PGRS family proteins. Obviously, the PE/PPE/PE-PGRS family proteins were the main targets of positive selection. The functional discussion of our findings implied that those positively selected genes were highly involved in antigen variations and immune evasions of Mycobacterium tuberculosis.
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PMID:Genes under positive selection in Mycobacterium tuberculosis. 2200 Aug 3