Linked Life Data

7641704

Source:http://linkedlifedata.com/resource/pubmed/id/7641704

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-9-18
pubmed:abstractText
Previous studies of doxorubicin-induced mutations employing F' lacl/lacO as an endogenous gene target have focused on properties of large deletions with 3' endpoints residing in the lacO region of the target gene. This study considers the influence of Lac repressor binding on the distribution of these deletions. Results of the DNA sequence level analysis of spontaneous and doxorubicin-induced i-d and lacO mutations in Escherichia coli uvrB- are reported for mutants isolated under conditions where Lac repression is relieved by isopropyl-beta-D-thiogalactopyranosid (IPTG; an inducer that prevents repressor binding to lacO). The location of deletions isolated from doxorubicin-treated cultures in the presence and absence of IPTG suggests that doxorubicin preferentially focuses deletion endpoints adjacent to its binding sites in lacO and that the distribution of these deletion endpoints is not modulated by Lac repressor binding. In contrast, spontaneous deletion endpoints are preferentially clustered in the loop away from the palindromic sequences under conditions of repression. However, when the Lac repressor/lacO binding complex is dissociated by IPTG, the spontaneous 3'-deletion endpoints distribute proportionally between the putative stem and loop of the lacO palindrome. The single most striking effect of IPTG induction of the Lac operon was elimination of a "hot spot" for T:A-->C:G transitions at position +6 in lacO. This base substitution "hot spot," which accounted for 17.6% of total doxorubicin-induced mutants and 16.4% of spontaneous mutants in repressed bacterial cultures, accounted for approximately 1% of total mutations in similar experiments carried out in the presence of IPTG. A large number of mutations at the +6 position are induced only by doxorubicin in the absence of IPTG, however, suggesting that both doxorubicin-induced and spontaneous mutation at this transition "hot spot" are mediated by Lac repressor binding to lacO.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0893-6692
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:geneSymbol
uvrB
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16-25
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7641704-Bacterial Proteins, pubmed-meshheading:7641704-Base Composition, pubmed-meshheading:7641704-Base Sequence, pubmed-meshheading:7641704-Doxorubicin, pubmed-meshheading:7641704-Enzyme Induction, pubmed-meshheading:7641704-Escherichia coli, pubmed-meshheading:7641704-Escherichia coli Proteins, pubmed-meshheading:7641704-Genes, Bacterial, pubmed-meshheading:7641704-Isopropyl Thiogalactoside, pubmed-meshheading:7641704-Lac Operon, pubmed-meshheading:7641704-Lac Repressors, pubmed-meshheading:7641704-Molecular Sequence Data, pubmed-meshheading:7641704-Mutagens, pubmed-meshheading:7641704-Point Mutation, pubmed-meshheading:7641704-Repressor Proteins, pubmed-meshheading:7641704-Sequence Deletion, pubmed-meshheading:7641704-Species Specificity, pubmed-meshheading:7641704-beta-Galactosidase
pubmed:year
1995
pubmed:articleTitle
Effect of isopropyl-beta-D-thiogalactopyranosid induction of the lac operon on the specificity of spontaneous and doxorubicin-induced mutations in Escherichia coli.
pubmed:affiliation
Department of Medicine, Case Western Reserve University, Ireland Cancer Center of University Hospitals, Cleveland, OH 44106, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't