| Full text | |
| Author(s): |
Quintero-Ruiz, Nathalia
;
Corradi, Camila
;
Moreno, Natalia Cestari
;
de Souza, Tiago Antonio
;
Menck, Carlos Frederico Martins
Total Authors: 5
|
| Document type: | Journal article |
| Source: | PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES; v. 24, n. 3, p. 21-pg., 2025-03-10. |
| Abstract | |
Skin cancer is associated with genetic mutations caused by sunlight exposure, primarily through ultraviolet (UV) radiation that damages DNA. While UVA is less energetic, it is the predominant solar UV component reaching the Earth's surface. However, the mechanisms of UVA-induced mutagenesis and its role in skin cancer development remain poorly understood. This study employed whole exome sequencing of clones from human XP-C cells, which lack nucleotide excision repair (NER), to characterize somatic mutations induced by UVA exposure. DNA sequence analysis of UVA-irradiated XP-C cells revealed a marked increase in mutation frequency across nearly all types of base substitutions, with particular enrichment in C > T transitions within the CCN and TCN trinucleotide context-potential sites for pyrimidine dimer formation. The C > T mutation primarily occurred at the 3 ' base of the 5 ' TC dimer, and an enrichment of CC > TT tandem mutations. We also identified the SBS7b COSMIC mutational signature within irradiated cells, which has been associated with tumors in sun-exposed skin. C > A transversions, often linked to oxidized guanine, were the second most frequently induced mutation, although a specific context for this base substitution was not identified. Moreover, C > T mutations were significantly increased in unirradiated XP-C compared to NER-proficient cells, which may be caused by unrepaired spontaneous DNA damage. Thus, this study indicates that pyrimidine dimers are the primary lesions contributing to UVA-induced mutagenesis in NER-deficient human cells and demonstrates that UVA generates mutational signatures similar to those of UVB irradiation. (AU) | |
| FAPESP's process: | 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg) |
| Grantee: | Carlos Frederico Martins Menck |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 14/15982-6 - Consequences of repair deficiencies in damaged genome |
| Grantee: | Carlos Frederico Martins Menck |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center |
| Grantee: | Mayana Zatz |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |