Mutagenicity Profile Induced by UVB Light in Human Xeroderma Pigmentosum Group C Cells(dagger)

Author(s)

Quintero-Ruiz, Nathalia ^[1] ; Corradi, Camila ^[1] ; Moreno, Natalia Cestari ^{[2, 1]} ; de Souza, Tiago Antonio ^{[1, 3]} ; Pereira Castro, Ligia ^[1] ; Rocha, Clarissa Ribeiro Reily ^{[1, 4]} ; Menck, Carlos Frederico Martins ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Lab Reparo DNA, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

^[3] Tau GC Bioinformat, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Dept Oncol Clin & Expt, Drug Resistance & Mutagenesis Lab, Escola Paulista Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: Photochemistry and Photobiology; SEP 2021.
• Web of Science Citations: 0

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. (AU)

• 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
• 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