The key role of UVA-light induced oxidative stress in human Xeroderma pigmentosum variant cells
| Autor: | Camila Corradi, Alessandra Luiza Pelegrini, Clarissa Ribeiro Reily Rocha, Veridiana Munford, Camila Carrião Machado Garcia, Carlos Frederico Martins Menck, Alain Sarasin, Natália Cestari Moreno |
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| Rok vydání: | 2019 |
| Předmět: |
DNA Replication
0301 basic medicine Xeroderma pigmentosum Cell cycle checkpoint DNA Repair Cell Survival Ultraviolet Rays DNA damage DNA polymerase DNA repair medicine.disease_cause Biochemistry Protein Carbonylation 03 medical and health sciences Onium Compounds 0302 clinical medicine Physiology (medical) medicine Humans Cytotoxicity Cell Line Transformed Xeroderma Pigmentosum biology Chemistry Nocodazole CARCINOGÊNESE Fibroblasts medicine.disease Acetylcysteine Cell biology Oxidative Stress 030104 developmental biology S Phase Cell Cycle Checkpoints biology.protein sense organs Carcinogenesis 030217 neurology & neurosurgery Oxidative stress DNA Damage |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | The UVA component of sunlight induces DNA damage, which are basically responsible for skin cancer formation. Xeroderma Pigmentosum Variant (XP-V) patients are defective in the DNA polymerase pol eta that promotes translesion synthesis after sunlight-induced DNA damage, implying in a clinical phenotype of increased frequency of skin cancer. However, the role of UVA-light in the carcinogenesis of these patients is not completely understood. The goal of this work was to characterize UVA-induced DNA damage and the consequences to XP-V cells, compared to complemented cells. DNA damage were induced in both cells by UVA, but lesion removal was particularly affected in XP-V cells, possibly due to the oxidation of DNA repair proteins, as indicated by the increase of carbonylated proteins. Moreover, UVA irradiation promoted replication fork stalling and cell cycle arrest in the S-phase for XP-V cells. Interestingly, when cells were treated with the antioxidant N-acetylcysteine, all these deleterious effects were consistently reverted, revealing the role of oxidative stress in these processes. Together, these results strongly indicate the crucial role of oxidative stress in UVA-induced cytotoxicity and are of interest for the protection of XP-V patients. |
| Databáze: | OpenAIRE |
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