Two structurally related diaziridinylbenzoquinones preferentially cross-link DNA at different sites upon reduction with DT-diaphorase.

2.50
Hdl Handle:
http://hdl.handle.net/10541/100397
Title:
Two structurally related diaziridinylbenzoquinones preferentially cross-link DNA at different sites upon reduction with DT-diaphorase.
Authors:
Berardini, M D; Souhami, R L; Lee, C S; Gibson, N W; Butler, John; Hartley, John A
Abstract:
The nucleotide sequence preferences for the formation of interstrand cross-links induced in DNA by 2,5-diaziridinyl-1,4-benzoquinone (DZQ) and 3,6-dimethyl-2,5-diaziridinyl-1,4-benzoquinone (MeDZQ) were studied using synthetic duplex oligonucleotides and denaturing polyacrylamide gel electrophoresis (PAGE). Reaction of these bifunctional alkylating agents with a DNA duplex containing several potential cross-linking sites resulted in the formation of cross-linked DNAs with different electrophoretic mobilities. Analysis of the principal cross-linked products by piperidine fragmentation revealed that the preferential site of cross-linking was altered from a 5'-GNC to a 5'-GC sequence upon reduction of DZQ to the hydroquinone form by the enzyme DT-diaphorase. In contrast, the reduced form of MeDZQ was found to preferentially cross-link at 5'-GNC sites within the same sequence. These preferences were confirmed in duplex oligonucleotides containing single potential cross-linking sites. Additional minor cross-linked products were characterized and revealed that DZQ and MeDZQ are both capable of cross-linking across four base pairs in a 5'-GNNC sequence.
Affiliation:
Department of Oncology, University College & Middlesex School of Medicine, London, U.K.
Citation:
Two structurally related diaziridinylbenzoquinones preferentially cross-link DNA at different sites upon reduction with DT-diaphorase. 1993, 32 (13):3306-12 Biochemistry
Journal:
Biochemistry
Issue Date:
6-Apr-1993
URI:
http://hdl.handle.net/10541/100397
DOI:
10.1021/bi00064a013
PubMed ID:
8461296
Type:
Article
Language:
en
ISSN:
0006-2960
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBerardini, M Den
dc.contributor.authorSouhami, R Len
dc.contributor.authorLee, C Sen
dc.contributor.authorGibson, N Wen
dc.contributor.authorButler, Johnen
dc.contributor.authorHartley, John Aen
dc.date.accessioned2010-06-07T10:30:57Z-
dc.date.available2010-06-07T10:30:57Z-
dc.date.issued1993-04-06-
dc.identifier.citationTwo structurally related diaziridinylbenzoquinones preferentially cross-link DNA at different sites upon reduction with DT-diaphorase. 1993, 32 (13):3306-12 Biochemistryen
dc.identifier.issn0006-2960-
dc.identifier.pmid8461296-
dc.identifier.doi10.1021/bi00064a013-
dc.identifier.urihttp://hdl.handle.net/10541/100397-
dc.description.abstractThe nucleotide sequence preferences for the formation of interstrand cross-links induced in DNA by 2,5-diaziridinyl-1,4-benzoquinone (DZQ) and 3,6-dimethyl-2,5-diaziridinyl-1,4-benzoquinone (MeDZQ) were studied using synthetic duplex oligonucleotides and denaturing polyacrylamide gel electrophoresis (PAGE). Reaction of these bifunctional alkylating agents with a DNA duplex containing several potential cross-linking sites resulted in the formation of cross-linked DNAs with different electrophoretic mobilities. Analysis of the principal cross-linked products by piperidine fragmentation revealed that the preferential site of cross-linking was altered from a 5'-GNC to a 5'-GC sequence upon reduction of DZQ to the hydroquinone form by the enzyme DT-diaphorase. In contrast, the reduced form of MeDZQ was found to preferentially cross-link at 5'-GNC sites within the same sequence. These preferences were confirmed in duplex oligonucleotides containing single potential cross-linking sites. Additional minor cross-linked products were characterized and revealed that DZQ and MeDZQ are both capable of cross-linking across four base pairs in a 5'-GNNC sequence.en
dc.language.isoenen
dc.subject.meshAlkylation-
dc.subject.meshAziridines-
dc.subject.meshBase Sequence-
dc.subject.meshBenzoquinones-
dc.subject.meshCross-Linking Reagents-
dc.subject.meshDNA-
dc.subject.meshGuanine-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshNAD(P)H Dehydrogenase (Quinone)-
dc.subject.meshOligodeoxyribonucleotides-
dc.subject.meshOxidation-Reduction-
dc.titleTwo structurally related diaziridinylbenzoquinones preferentially cross-link DNA at different sites upon reduction with DT-diaphorase.en
dc.typeArticleen
dc.contributor.departmentDepartment of Oncology, University College & Middlesex School of Medicine, London, U.K.en
dc.identifier.journalBiochemistryen
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