UVA irradiation of BrU-substituted DNA in the presence of Hoechst 33258
| Autor: | Hiroshi Sugiyama, Zutao Yu, Ji Hoon Han, Seiichiro Kizaki, Abhijit Saha |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
5-Bromouracil DNA repair Clinical Biochemistry Pharmaceutical Science Context (language use) Biochemistry Electron transfer 03 medical and health sciences chemistry.chemical_compound Bromouracil Drug Discovery Nucleosome DNA photoreaction Molecular Biology Micro-irradiation 030102 biochemistry & molecular biology Chemistry Organic Chemistry Linker DNA Molecular biology Bisbenzimidazole 030104 developmental biology Biophysics Molecular Medicine biological phenomena cell phenomena and immunity DNA |
| Zdroj: | Bioorganic & Medicinal Chemistry. 26:37-40 |
| ISSN: | 0968-0896 |
| Popis: | Given that our knowledge of DNA repair is limited because of the complexity of the DNA system, a technique called UVA micro-irradiation has been developed that can be used to visualize the recruitment of DNA repair proteins at double-strand break (DSB) sites. Interestingly, Hoechst 33258 was used under micro-irradiation to sensitize 5-bromouracil (BrU)-labelled DNA, causing efficient DSBs. However, the molecular basis of DSB formation under UVA micro-irradiation remains unknown. Herein, we investigated the mechanism of DSB formation under UVA micro-irradiation conditions. Our results suggest that the generation of a uracil-5-yl radical through electron transfer from Hoechst 33258 to BrU caused DNA cleavage preferentially at self-complementary 5′-AABrUBrU-3′ sequences to induce DSB. We also investigated the DNA cleavage in the context of the nucleosome to gain a better understanding of UVA micro-irradiation in a cell-like model. We found that DNA cleavage occurred in both core and linker DNA regions although its efficiency reduced in core DNA. |
| Databáze: | OpenAIRE |
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