Mutagenicity Profile Induced by UVB Light in Human Xeroderma Pigmentosum Group C Cells †

Autor: Tiago Antonio de Souza, Carlos Frederico Martins Menck, Clarissa Ribeiro Reily Rocha, Camila Corradi, Natália Cestari Moreno, Ligia Pereira Castro, Nathalia Quintero-Ruiz
Rok vydání: 2021
Předmět:
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 1751-1097
0031-8655
DOI: 10.1111/php.13516
Popis: 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 non-affected individuals.
Databáze: OpenAIRE
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