The key role of UVA-light induced oxidative stress in human Xeroderma Pigmentosum Variant cells

Author(s)

Moreno, Natalia Cestari ^[1] ; Machado Garcia, Camila Carriao ^{[2, 3]} ; Munford, Veridiana ^[1] ; Reily Rocha, Clarissa Ribeiro ^[1] ; Pelegrini, Alessandra Luiza ^[1] ; Corradi, Camila ^[1] ; Sarasin, Alain ^[4] ; Martins Menck, Carlos Frederico ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo, SP - Brazil

^[2] Univ Fed Ouro Preto, Dept Biol Sci, Ouro Preto, MG - Brazil

^[3] Univ Fed Ouro Preto, NUPEB, Ouro Preto, MG - Brazil

^[4] Univ Paris Sud, Inst Gustave Roussy, CNRS, Lab Genet Instabil & Oncogenesis, UMR8200, Villejuif - France

• Document type: Journal article
• Source: Free Radical Biology and Medicine; v. 131, p. 432-442, FEB 1 2019.
• Web of Science Citations: 3

Abstract

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. (AU)

• 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: 12/16929-6 - Effect of UVA light in cells from patients with variant Xeroderma pigmentosum
• Grantee: Natália Cestari Moreno
• Support Opportunities: Scholarships in Brazil - Doctorate