Article
Mutation E522K in human DNA topoisomerase IIbeta confers resistance to methyl N-(4'-(9-acridinylamino)-phenyl)carbamate hydrochloride and methyl N-(4'-(9-acridinylamino)-3-methoxy-phenyl) methane sulfonamide but hypersensitivity to etoposide.
Molecular pharmacology - 1 Sept 2004
Leontiou Chrysoula, Lakey Jeremy H, Austin Caroline A
Abstract excerpt
Human cells express two isoforms of topoisomerase II, alpha and beta, that are both targeted by anticancer drugs. To investigate acridine resistance mediated by topoisomerase IIbeta, we used a forced molecular evolution approach. A library of mutated topoisomerase IIbeta cDNAs was generated by hydroxylamine mutagenesis and was transformed into the yeast JN394 top2-4. Methyl...
Topics
- Amino Acid Sequence
- Amsacrine
- Antineoplastic Agents
- DNA
- DNA Topoisomerases, Type II
- Enzyme Stability
- Etoposide
- Glutamic Acid
- Humans
- Lysine
- Models, Molecular
- Mutation
- Topoisomerase II Inhibitors
- Tranexamic Acid