Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1983-5-5
pubmed:abstractText
The effects of intercalating agents on the fidelity of DNA synthesis in vitro have been investigated. The accuracy of DNA synthesis with Escherichia coli DNA polymerase I with both the poly[d(A-T)] and poly[d(G-C)] templates is decreased in the presence of the intercalating agents proflavin, ethidium bromide, acridine orange, ICR-170, and ICR-191. Nearest neighbor analyses of the product of the reaction indicate that two different types of misincorporations occur in the presence of intercalating agents, frameshifts, and single-base substitutions. With alternating polynucleotide templates, frameshifts involving pyrimidines are the most frequent change in sequence observed. Overall, frameshift misincorporations occur with frequencies of one complementary pyrimidine for each intercalated site and one noncomplementary pyrimidine for each 150 sites. From analysis of nearest neighbor frequencies in the product, it is inferred that the intercalating agents interact specifically with pyrimidine (3' leads to 5') purine sequences. An analysis of ratios of correct nucleotide incorporations as a function of intercalator concentration indicates that frameshifts are predominantly additions; however, one cannot rule out infrequent deletions. Base substitutions in the presence of intercalators occur less frequently than frameshifts. From the results of reaction kinetics and nearest neighbor frequencies, it is concluded that the noncomplementary nucleotides are incorporated in phosphodiester linkage and are present as single-base substitutions. Taken together, the results of these studies suggest at least two different modes of action for intercalating agents on the accuracy of DNA synthesis: one leading to frameshift misincorporations and the other leading to single-base substitutions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
258
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4477-84
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1983
pubmed:articleTitle
On the fidelity of DNA replication. Specificity of nucleotide substitution by intercalating agents.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.