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

Photochem Photobiol

Laboratorio de reparo de DNA, Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

Published: May 2022

AI Article Synopsis

  • * Researchers compared mutagenesis patterns in NER-proficient human skin cells to XP-C-deficient cells (which can't repair DNA) after UVB exposure, finding higher mutation rates in the XP-C cells, particularly C>T transitions.
  • * The study's results mirror mutation patterns found in human skin cancer tumors, suggesting it could inform our understanding of how mutations occur in both affected and unaffected individuals.

Article Abstract

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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Source
http://dx.doi.org/10.1111/php.13516DOI Listing

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