Linked Life Data

1986269

Source:http://linkedlifedata.com/resource/pubmed/id/1986269

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-2-8
pubmed:abstractText
The antifolate, trimethoprim (TRMP, 5 microM) caused a 10-fold increase in mutation frequency and primarily induced base substitution and deletion mutations in wild-type E. coli. Base-substitutions induced by antifolates were equally divided between transition and transversion mutations. When mutations consistent with expected antifolate-induced deoxynucleotide pool imbalances were considered, 29 out of 32 base-substitution mutations in the i-d region of the lacI gene were followed 3' by the same nucleotide substituted at the base mismatch site and all but one mutation occurred at sites consistent with next nucleotide effects resulting from antifolate-induced deoxynucleotide pool alterations. 66% of the TRMP-induced base-substitutions were also found at sites of frequent mutation identified in the spontaneous spectrum of a mutator D5 strain of E. coli which is deficient in the 3'-exonucleolytic proofreading function of DNA polymerase III holoenzyme. These results suggest that the pool imbalances induced by the antifolate trimethoprim compromise the proofreading activity of polymerase III holoenzyme and lead to mutation at specific sites. The results also imply that not all DNA sequence environments encountered by DNA polymerase III holoenzyme and its accompanying exonuclease are handled with equal facility at the level of nucleotide insertion and exonucleolytic proofreading when the enzyme is faced with an intracellular nucleotide pool imbalance. A number of small deletion and duplication mutations were also induced by the antifolate trimethoprim. In most cases these mutations were flanked by at least two A:T base pairs which could facilitate DNA-strand breakage at deoxyuridine misincorporation sites.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:volume
246
pubmed:geneSymbol
lacO
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
75-91
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Specificities mediated by neighboring nucleotides appear to underlie mutation induced by antifolates in E. coli.
pubmed:affiliation
Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland, OH.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't