Genome-Wide Adductomics Analysis Reveals Heterogeneity in the Induction and Loss of Cyclobutane Thymine Dimers across Both the Nuclear and Mitochondrial Genomes
| Autor: | Alaa S Alhegaili, Nicolas Sylvius, Mahsa Karbaschi, Matthew Blades, George D. D. Jones, Helen G. Tempest, Marcus S. Cooke, Yunhee Ji |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Mitochondrial DNA
Cell Survival DNA repair DNA damage dna repair Pyrimidine dimer Biology Genome Article Catalysis DNA sequencing Inorganic Chemistry lcsh:Chemistry Genetic Heterogeneity 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physical and Theoretical Chemistry uv radiation Molecular Biology lcsh:QH301-705.5 Spectroscopy 030304 developmental biology genome analysis next generation sequencing 0303 health sciences Organic Chemistry High-Throughput Nucleotide Sequencing General Medicine 3. Good health Computer Science Applications Nuclear DNA Cell biology chemistry lcsh:Biology (General) lcsh:QD1-999 Pyrimidine Dimers 030220 oncology & carcinogenesis Genome Mitochondrial dna damage Cyclobutanes DNA Genome-Wide Association Study |
| Zdroj: | International Journal of Molecular Sciences, Vol 20, Iss 20, p 5112 (2019) International Journal of Molecular Sciences Volume 20 Issue 20 |
| ISSN: | 1422-0067 |
| Popis: | The distribution of DNA damage and repair is considered to occur heterogeneously across the genome. However, commonly available techniques, such as the alkaline comet assay or HPLC-MS/MS, measure global genome levels of DNA damage, and do not reflect potentially significant events occurring at the gene/sequence-specific level, in the nuclear or mitochondrial genomes. We developed a method, which comprises a combination of Damaged DNA Immunoprecipitation and next generation sequencing (DDIP-seq), to assess the induction and repair of DNA damage induced by 0.1 J/cm2 solar-simulated radiation at the sequence-specific level, across both the entire nuclear and mitochondrial genomes. DDIP-seq generated a genome-wide, high-resolution map of cyclobutane thymine dimer (T< > T) location and intensity. In addition to being a straightforward approach, our results demonstrated a clear differential distribution of T< T induction and loss, across both the nuclear and mitochondrial genomes. For nuclear DNA, this differential distribution existed at both the sequence and chromosome level. Levels of T< T were much higher in the mitochondrial DNA, compared to nuclear DNA, and decreased with time, confirmed by qPCR, despite no reported mechanisms for their repair in this organelle. These data indicate the existence of regions of sensitivity and resistance to damage formation, together with regions that are fully repaired, and those for which > 90% of damage remains, after 24 h. This approach offers a simple, yet more detailed approach to studying cellular DNA damage and repair, which will aid our understanding of the link between DNA damage and disease. |
| Databáze: | OpenAIRE |
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