Linked Life Data

1696837

Source:http://linkedlifedata.com/resource/pubmed/id/1696837

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
1990-9-27
pubmed:abstractText
The antitumor agent camptothecin stabilizes type I topoisomerase-DNA complexes. One of the primary cellular responses to camptothecin exposure is rapid cessation of RNA synthesis. Results obtained by using an in vitro transcription system supplemented with eukaryotic topoisomerase I show that this inhibition can be attributed to physical blockage of the RNA polymerase by camptothecin-stabilized topoisomerase I-DNA complexes on the DNA template. The site of premature termination is located 10 base pairs upstream of the topoisomerase I linked nucleotide residue on the coding strand, corresponding closely to the border of the protected area obtained in a micrococcus nuclease footprint of topoisomerase I. The RNA polymerase transcribes unimpeded through complexes attached to the noncoding strand. No inhibitory effect of camptothecin on RNA transcription was observed with human topoisomerase I isolated from a camptothecin-resistant cell line. Taken together, the data suggest that part of the cytotoxicity of camptothecin is mediated through adduct formation on transcribed DNA, resulting in interference with transcriptional elongation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5613-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Camptothecin-stabilized topoisomerase I-DNA adducts cause premature termination of transcription.
pubmed:affiliation
Department of Molecular Biology and Plant Physiology, University of Aarhus, Denmark.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't