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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
|
pubmed:dateCreated |
1992-3-31
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pubmed:abstractText |
Cloning and sequencing of cDNA segments of human TOP2 gene encoding the 170 kDa form of human DNA topoisomerase II show that Arg486 of the enzyme has been mutated to a lysine in the enzyme from two human leukemia cell lines HL-60/AMSA and KBM-3/AMSA, which were independently selected for resistance to the antitumor drug amsacrine (4'-[9-acridinylamino]-methanesulfon-m-anisidide, mAMSA). Sequence identity comparisons between eukaryotic DNA topoisomerase II and bacterial gyrase (bacterial DNA topoisomerase II) indicate that the position of the common mutation observed in mAMSA-resistant human TOP2 corresponds to that of the point mutation nal-31 in the Escherichia coli gyrase B gene, which confers resistance to nalidixic acid. Because mAMSA and nalidixic acid are known to act on their respective targets by a common mechanism of trapping the covalent enzyme-DNA intermediates, these results provide strong evidence that the 170 kDa form of human DNA topoisomerase II is a major cellular target of mAMSA, and that Arg486 of this enzyme is involved in mAMSA-mediated trapping of the covalent enzyme-DNA complex.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
|
pubmed:issn |
0022-2836
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
20
|
pubmed:volume |
223
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
837-43
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:1311390-Amino Acid Sequence,
pubmed-meshheading:1311390-Amsacrine,
pubmed-meshheading:1311390-DNA Mutational Analysis,
pubmed-meshheading:1311390-DNA Topoisomerases, Type II,
pubmed-meshheading:1311390-Humans,
pubmed-meshheading:1311390-Molecular Sequence Data,
pubmed-meshheading:1311390-Molecular Weight,
pubmed-meshheading:1311390-Polymerase Chain Reaction,
pubmed-meshheading:1311390-Polymorphism, Genetic,
pubmed-meshheading:1311390-Restriction Mapping,
pubmed-meshheading:1311390-Topoisomerase II Inhibitors,
pubmed-meshheading:1311390-Tumor Cells, Cultured
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pubmed:year |
1992
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pubmed:articleTitle |
Two independent amsacrine-resistant human myeloid leukemia cell lines share an identical point mutation in the 170 kDa form of human topoisomerase II.
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pubmed:affiliation |
Division of Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston 77030.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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