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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-6-27
pubmed:abstractText
Transcription of DNA opens the chromatin, causes topological changes in DNA and transiently exposes the two strands to different biochemical environments. Consequently, it has long been argued that transcription may promote damage to DNA and there are data in Escherichia coli and yeast supporting a correlation between high transcription and mutations. We examined the transcription-dependence of the reversion of a nonsense codon (TGA) in E. coli and found that there was a strong dependence of mutations on transcription in strains defective in the repair of 8-oxoguanine in DNA. Under conditions of high transcription there was a three to five-fold increase in mutations that changed TGA in the non-transcribed strand to a sense codon. Furthermore, in both mutY and mutM mutY backgrounds the mutations were overwhelmingly G:C to T:A. In contrast, when the TGA was in the transcribed strand in relation with the inducible promoter, high transcription decreased the rate of reversion. Similar results were obtained in a strain defective in the transcription-repair coupling factor, Mfd, suggesting that transcription dependent increase in base substitutions does not require transcription-dependent DNA repair. However, Mfd does modulate the magnitude of the mutagenic effect of transcription. These data are consistent with a model in which the non-transcribed strand is more susceptible to oxidative damage during transcription than the transcribed strand. These results suggest that the magnitudes of individual base substitutions and their relative numbers in other studies of mutational spectra may also be affected by transcription.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1568-7864
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
806-13
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Transcription promotes guanine to thymine mutations in the non-transcribed strand of an Escherichia coli gene.
pubmed:affiliation
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
pubmed:publicationType
Journal Article