Journal
PHOTOCHEMISTRY AND PHOTOBIOLOGY
Volume 98, Issue 3, Pages 713-731Publisher
WILEY
DOI: 10.1111/php.13516
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Funding
- Sao Paulo Research Foundation (FAPESP, SP, Brazil)
- The Netherlands Organization for Scientific Research (NWO, The Netherlands) (FAPESP) [2019/19435-3, 2013/08028-1]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [308868/2018-8]
- CoordenacAo de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brasilia, DF, Brazil) [001]
- Administrative Department of Science, Technology and Innovation of Colombia (COLCIENCIAS, Bogota, Colombia)
- NGS, at the Core Facility for Scientific Research - USP (CEFAP-USP/GENIAL)
- Multi-user genomic Section of the Human Genome & Stem Cell Research Center (HUG-CELL)
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Nucleotide excision repair (NER) is crucial for genome protection from UVB-induced mutations, as seen in XP-C-deficient cells which exhibit a mutation spectrum similar to human skin cancer.
Nucleotide excision repair (NER) is one of the main pathways for genome protection against structural DNA damage caused by sunlight, which in turn is extensively related to skin cancer development. The mutation spectra induced by UVB were investigated by whole-exome sequencing of randomly selected clones of NER-proficient and XP-C-deficient human skin fibroblasts. As a model, a cell line unable to recognize and remove lesions (XP-C) was used and compared to the complemented isogenic control (COMP). As expected, a significant increase of mutagenesis was observed in irradiated XP-C cells, mainly C>T transitions, but also CC>TT and C>A base substitutions. Remarkably, the C>T mutations occur mainly at the second base of dipyrimidine sites in pyrimidine-rich sequence contexts, with 5 ' TC sequence the most mutated. Although T>N mutations were also significantly increased, they were not directly related to pyrimidine dimers. Moreover, the large-scale study of a single UVB irradiation on XP-C cells allowed recovering the typical mutation spectrum found in human skin cancer tumors. Eventually, the data may be used for comparison with the mutational profiles of skin tumors obtained from XP-C patients and may help to understand the mutational process in nonaffected individuals.
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