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dc.contributor.authorGonzaga, P E
dc.contributor.authorHarris, Linda
dc.contributor.authorMargison, Geoffrey P
dc.contributor.authorBrent, T P
dc.date.accessioned2010-08-18T08:47:37Z
dc.date.available2010-08-18T08:47:37Z
dc.date.issued1990-07-11
dc.identifier.citationEvidence that covalent complex formation between BCNU-treated oligonucleotides and E. coli alkyltransferases requires the O6-alkylguanine function. 1990, 18 (13):3961-6 Nucleic Acids Res.en
dc.identifier.issn0305-1048
dc.identifier.pmid2197601
dc.identifier.doi10.1093/nar/18.13.3961
dc.identifier.urihttp://hdl.handle.net/10541/109802
dc.description.abstractChloroethylnitrosoureas (CENUs) are thought to induce cytotoxic DNA interstrand cross-links via an initial reaction at O6-position of guanine, yielding a rearranged intermediate, O6,N1-ethanoguanine. Repair of these adducts by mammalian and bacterial DNA alkyltransferases blocks the formation of cross-links. Human alkyltransferase can form a covalent complex with DNA containing BCNU-induced cross-link precursors, but the nature of the DNA-protein linkage remains unknown. Using E. coli alkyltransferases expressed by the ada and ogt genes, we now demonstrate that both enzymes can form such complexes with CENU-treated DNA. We attribute this reaction to the O6-alkylguanine repair function, because an N-terminal fragment of the ada protein, which has only alkylphosphotriester repair activity, failed to form a similar complex. This result is consistent with the idea that complex formation requires an alkyltransferase reaction with a guanine adduct, such as O6,N1-ethanoguanine. It tends to exclude the possibility that such reactions simply involve alkylation of the enzyme by reactive DNA adducts such as chloroethylphosphate or chloroethylguanine.
dc.language.isoenen
dc.subject.meshBase Sequence
dc.subject.meshCarmustine
dc.subject.meshElectrophoresis, Polyacrylamide Gel
dc.subject.meshEscherichia coli
dc.subject.meshGuanine
dc.subject.meshHumans
dc.subject.meshMethyltransferases
dc.subject.meshMolecular Sequence Data
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase
dc.subject.meshOligodeoxyribonucleotides
dc.titleEvidence that covalent complex formation between BCNU-treated oligonucleotides and E. coli alkyltransferases requires the O6-alkylguanine function.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemical and Clinical Pharmacology, St Jude Children's Research Hospital, Memphis, TN 38101.en
dc.identifier.journalNucleic Acids Researchen
html.description.abstractChloroethylnitrosoureas (CENUs) are thought to induce cytotoxic DNA interstrand cross-links via an initial reaction at O6-position of guanine, yielding a rearranged intermediate, O6,N1-ethanoguanine. Repair of these adducts by mammalian and bacterial DNA alkyltransferases blocks the formation of cross-links. Human alkyltransferase can form a covalent complex with DNA containing BCNU-induced cross-link precursors, but the nature of the DNA-protein linkage remains unknown. Using E. coli alkyltransferases expressed by the ada and ogt genes, we now demonstrate that both enzymes can form such complexes with CENU-treated DNA. We attribute this reaction to the O6-alkylguanine repair function, because an N-terminal fragment of the ada protein, which has only alkylphosphotriester repair activity, failed to form a similar complex. This result is consistent with the idea that complex formation requires an alkyltransferase reaction with a guanine adduct, such as O6,N1-ethanoguanine. It tends to exclude the possibility that such reactions simply involve alkylation of the enzyme by reactive DNA adducts such as chloroethylphosphate or chloroethylguanine.


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