Complex interplay of lesion-specific DNA repair enzyme on bistranded clustered DNA damage harboring Tg:G mismatch in nucleosome core particles
| Autor: | Bhavini Kumari, Prolay Das, Kislay K. Sinha |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Cell Extracts
0301 basic medicine DNA Repair DNA repair DNA damage medicine.disease_cause DNA Mismatch Repair General Biochemistry Genetics and Molecular Biology DNA Glycosylases Deoxyribonuclease (Pyrimidine Dimer) 03 medical and health sciences chemistry.chemical_compound Radiation Ionizing medicine Humans Nucleosome DNA Breaks Double-Stranded Carcinogen chemistry.chemical_classification 030102 biochemistry & molecular biology Deoxyguanosine 8-Hydroxy-2'-deoxyguanosine General Medicine Nucleosomes Oxidative Stress 030104 developmental biology Enzyme chemistry 8-Hydroxy-2'-Deoxyguanosine Biophysics General Agricultural and Biological Sciences Thymine DNA Oxidative stress DNA Damage HeLa Cells |
| Zdroj: | Journal of Biosciences. 43:575-583 |
| ISSN: | 0973-7138 0250-5991 |
| DOI: | 10.1007/s12038-018-9786-x |
| Popis: | 5,6-Dihydroxy-5,6-dihydrothymine (thymine glycol) and 7,8-dihydro-8-oxo-20-deoxyguanosine (8-oxodG) are major DNA damage lesions produced by endogenous oxidative stress, as well as inflicted by carcinogens and ionizing radiation. The processing of Tg:G mismatch and 8-oxodG in close proximity of each other in a bistranded clustered environment in DNA oligomer duplexes as well as in a nucleosome core particle (NCP) model are reported here. The processing of the lesions was evaluated by purified enzyme cocktails of hNTH1 and hOGG1 as well as with a HeLa cell extract. Interestingly, the yield of double-strand breaks (DSBs) resulting from the processing of the bistranded lesions are appreciably lower when the DNA is treated with the HeLa cell extract compared with the relevant purified enzyme cocktail in both models. Clustered bistranded lesions become more repair refractive when reconstituted as an NCP. This indicates a complex interplay between the repair enzymes that influence the processing of the bistranded cluster damage positively to avoid the formation of DSBs under cellular conditions. In addition to position and orientation of the lesions, the type of the lesions in the cluster environment in DNA along with the relative abundance of the lesion-specific enzymes in the cells strongly prevents the processing of the oxidized nucleobases. |
| Databáze: | OpenAIRE |
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