Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1992-9-18
|
| pubmed:abstractText |
In Escherichia coli, the miniF plasmid CcdB protein is responsible for cell death when its action is not prevented by polypeptide CcdA. We report the isolation, localization, sequencing and properties of a bacterial mutant resistant to the cytotoxic activity of the CcdB protein. This mutation is located in the gene encoding the A subunit of topoisomerase II and produces an Arg462----Cys substitution in the amino acid sequence of the GyrA polypeptide. Hence, the mutation was called gyrA462. We show that in the wild-type strain, the CcdB protein promotes plasmid linearization; in the gyrA462 strain, this double-stranded DNA cleavage is suppressed. This indicates that the CcdB protein is responsible for gyrase-mediated double-stranded DNA breakage. CcdB, in the absence of CcdA, induces the SOS pathway. SOS induction is a biological response to DNA-damaging agents. We show that the gyrA462 mutation suppresses this SOS activation, indicating that SOS induction is a consequence of DNA damages promoted by the CcdB protein on gyrase-DNA complexes. In addition, we observe that the CcdBS sensitive phenotype dominates over the resistant phenotype. This is better explained by the conversion, in gyrA+/gyrA462 merodiploid strains, of the wild-type gyrase into a DNA-damaging agent. These results strongly suggest that the CcdB protein, like quinolone antibiotics and a variety of antitumoral drugs, is a DNA topoisomerase II poison. This is the first proteinic poison-antipoison mechanism that has been found to act via the DNA topoisomerase II.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/CcdB protein, Plasmid F,
http://linkedlifedata.com/resource/pubmed/chemical/Cytotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Bacterial,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Gyrase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0022-2836
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
5
|
| pubmed:volume |
226
|
| pubmed:geneSymbol |
ccdA,
ccdB
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
735-45
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:1324324-Amino Acid Sequence,
pubmed-meshheading:1324324-Bacterial Proteins,
pubmed-meshheading:1324324-Bacterial Toxins,
pubmed-meshheading:1324324-Cell Death,
pubmed-meshheading:1324324-Cytotoxins,
pubmed-meshheading:1324324-DNA, Bacterial,
pubmed-meshheading:1324324-DNA Damage,
pubmed-meshheading:1324324-DNA Gyrase,
pubmed-meshheading:1324324-DNA Topoisomerases, Type II,
pubmed-meshheading:1324324-Escherichia coli,
pubmed-meshheading:1324324-F Factor,
pubmed-meshheading:1324324-Genes, Bacterial,
pubmed-meshheading:1324324-Macromolecular Substances,
pubmed-meshheading:1324324-Mutation,
pubmed-meshheading:1324324-Plasmids,
pubmed-meshheading:1324324-Protein Binding,
pubmed-meshheading:1324324-Recombination, Genetic,
pubmed-meshheading:1324324-Restriction Mapping,
pubmed-meshheading:1324324-SOS Response (Genetics)
|
| pubmed:year |
1992
|
| pubmed:articleTitle |
Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes.
|
| pubmed:affiliation |
Département de Biologie Moléculaire, Université Libre de Bruxelles, Belgium.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|