دورية أكاديمية
Genome-Wide DNA Alterations in X-Irradiated Human Gingiva Fibroblasts
العنوان: | Genome-Wide DNA Alterations in X-Irradiated Human Gingiva Fibroblasts |
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المؤلفون: | Neetika Nath, Lisa Hagenau, Stefan Weiss, Ana Tzvetkova, Lars R. Jensen, Lars Kaderali, Matthias Port, Harry Scherthan, Andreas W. Kuss |
المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 16, p 5778 (2020) |
بيانات النشر: | MDPI AG, 2020. |
سنة النشر: | 2020 |
المجموعة: | LCC:Biology (General) LCC:Chemistry |
مصطلحات موضوعية: | radiation doses, repair mechanism, translocation, transition transversion ratio, IR-induced variants, SNVs, Biology (General), QH301-705.5, Chemistry, QD1-999 |
الوصف: | While ionizing radiation (IR) is a powerful tool in medical diagnostics, nuclear medicine, and radiology, it also is a serious threat to the integrity of genetic material. Mutagenic effects of IR to the human genome have long been the subject of research, yet still comparatively little is known about the genome-wide effects of IR exposure on the DNA-sequence level. In this study, we employed high throughput sequencing technologies to investigate IR-induced DNA alterations in human gingiva fibroblasts (HGF) that were acutely exposed to 0.5, 2, and 10 Gy of 240 kV X-radiation followed by repair times of 16 h or 7 days before whole-genome sequencing (WGS). Our analysis of the obtained WGS datasets revealed patterns of IR-induced variant (SNV and InDel) accumulation across the genome, within chromosomes as well as around the borders of topologically associating domains (TADs). Chromosome 19 consistently accumulated the highest SNVs and InDels events. Translocations showed variable patterns but with recurrent chromosomes of origin (e.g., Chr7 and Chr16). IR-induced InDels showed a relative increase in number relative to SNVs and a characteristic signature with respect to the frequency of triplet deletions in areas without repetitive or microhomology features. Overall experimental conditions and datasets the majority of SNVs per genome had no or little predicted functional impact with a maximum of 62, showing damaging potential. A dose-dependent effect of IR was surprisingly not apparent. We also observed a significant reduction in transition/transversion (Ti/Tv) ratios for IR-dependent SNVs, which could point to a contribution of the mismatch repair (MMR) system that strongly favors the repair of transitions over transversions, to the IR-induced DNA-damage response in human cells. Taken together, our results show the presence of distinguishable characteristic patterns of IR-induced DNA-alterations on a genome-wide level and implicate DNA-repair mechanisms in the formation of these signatures. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1422-0067 1661-6596 |
Relation: | https://www.mdpi.com/1422-0067/21/16/5778; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
DOI: | 10.3390/ijms21165778 |
URL الوصول: | https://doaj.org/article/01f0ffdcd1c44ef0ba0e37b79c5f4f83 |
رقم الأكسشن: | edsdoj.01f0ffdcd1c44ef0ba0e37b79c5f4f83 |
قاعدة البيانات: | Directory of Open Access Journals |
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