Two structurally related diaziridinylbenzoquinones preferentially cross-link DNA at different sites upon reduction with DT-diaphorase.
AffiliationDepartment of Oncology, University College & Middlesex School of Medicine, London, U.K.
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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.
CitationTwo structurally related diaziridinylbenzoquinones preferentially cross-link DNA at different sites upon reduction with DT-diaphorase. 1993, 32 (13):3306-12 Biochemistry
- Molecular dynamics simulations provide a structural basis for the experimentally observed nucleotide preferences for DNA interstrand cross-links induced by aziridinylbenzoquinones.
- Authors: Haworth IS, Lee CS, Yuki M, Gibson NW
- Issue date: 1993 Nov 30
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- Authors: Lee CS, Hartley JA, Berardini MD, Butler J, Siegel D, Ross D, Gibson NW
- Issue date: 1992 Mar 24
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- Authors: Hartley JA, Berardini M, Ponti M, Gibson NW, Thompson AS, Thurston DE, Hoey BM, Butler J
- Issue date: 1991 Dec 17
- Mapping of DNA alkylation sites induced by aziridinylbenzoquinones in human cells by ligation-mediated polymerase chain reaction.
- Authors: Lee CS, Pfeifer GP, Gibson NW
- Issue date: 1994 Apr 1
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- Authors: Gibson NW, Hartley JA, Butler J, Siegel D, Ross D
- Issue date: 1992 Sep