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

Dihydrouracil (DHU) is a major base damage product formed from cytosine following exposure of DNA to ionizing radiation under anoxic conditions. To gain insight into the DNA lesion structural requirements for RNA polymerase arrest or bypass at various DNA damages located on the transcribed strand during elongation, DHU was placed onto promoter-containing DNA templates 20 nucleotides downstream from the transcription start site. In vitro, single-round transcription experiments carried out with SP6 and T7 RNA polymerases revealed that following a brief pause at the DHU site, both enzymes efficiently bypass this lesion with subsequent rapid generation of full-length runoff transcripts. Direct sequence analysis of these transcripts indicated that both RNA polymerases insert primarily adenine opposite to the DHU site, resulting in a G-to-A transition mutation in the lesion bypass product. Such bypass and insertion events at DHU sites (or other types of DNA damages), if they occur in vivo, have a number of important implications for both the repair of such lesions and the DNA damage-induced production of mutant proteins at the level of transcription (transcriptional mutagenesis).
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PMID:RNA polymerase bypass at sites of dihydrouracil: implications for transcriptional mutagenesis. 852 38

Dihydrouracil (DHU) is a DNA base damage product produced in significant amounts by ionizing radiation damage to cytosine under anoxic conditions. DHU represents a model for pyrimidine base damage (ring saturation products) of the type recognized and repaired by Escherichia coli endonuclease III and its homologs in other species. We have built this lesion into synthetic oligonucleotides, with DHU placed at a single location downstream from an E.coli RNA polymerase promoter. This construct was used to determine the effect of DHU when encountered on a DNA template strand by either E.coli RNA or DNA polymerase (Klenow fragment). Single round transcription experiments or primer extension-type replication experiments were conducted in order to make a direct comparison between RNA and DNA polymerases with DHU placed within the same sequence context. Both DNA and RNA polymerase efficiently bypass DHU and insert adenine opposite this lesion. These results suggest that DHU is mutagenic with respect to both replication and transcription and have implications for DNA repair as well the routes leading to generation of mutant proteins in dividing and non-dividing cells.
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PMID:Escherichia coli RNA and DNA polymerase bypass of dihydrouracil: mutagenic potential via transcription and replication. 951 42