Two structurally related diaziridinylbenzoquinones preferentially cross-link DNA at different sites upon reduction with DT-diaphorase
| Autor: | Mark D. Berardini, Neil W. Gibson, Robert L. Souhami, John Butler, John A. Hartley, Chong Soon Lee |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Guanine
Alkylation Base Sequence Oligonucleotide Chemistry Base pair Aziridines Molecular Sequence Data Nucleic acid sequence DNA Biochemistry chemistry.chemical_compound Cross-Linking Reagents Oligodeoxyribonucleotides Duplex (building) Nucleic acid Benzoquinones NAD(P)H Dehydrogenase (Quinone) A-DNA Polyacrylamide gel electrophoresis Oxidation-Reduction |
| Zdroj: | Biochemistry. 32(13) |
| ISSN: | 0006-2960 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|