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

Moreno, Natália Cestari; García, Camila; Munford, Veridiana; Rocha, Clarissa Ribeiro Reily; Pelegrini, Alessandra Luíza; Corradi, Camila; Sarasin, Alain; Menck, Carlos Frederico Martins

doi:10.1016/j.freeradbiomed.2018.12.012

Cited by 24 publications

(8 citation statements)

References 67 publications

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“…The experiments of host cell reactivation assay were performed as previously described 38,39 . Briefly, pHIV-dTomato (Addgene #21374, Cambridge, MA, USA) plasmid was irradiated with 600 J/m 2 of UVC light or incubated with 750 nM cisplatin for 3 h at 37 °C to induce DNA damage.…”

Section: Methodsmentioning

confidence: 99%

The balance between NRF2/GSH antioxidant mediated pathway and DNA repair modulates cisplatin resistance in lung cancer cells

Silva

Rocha

Kinker

et al. 2019

Sci Rep

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Lung cancer patients face a dismal prognosis mainly due to the low efficacy of current available treatments. Cisplatin is the first-line chemotherapy treatment for those patients, however, resistance to this drug is a common and yet not fully understood phenomenon. Aiming to shed new light into this puzzle, we used established normal and malignant lung cell lines displaying different sensitivity towards cisplatin treatment. We observed a negative correlation between cell viability and DNA damage induction upon cisplatin treatment. Interestingly, drug sensitivity in those cell lines was not due to either difference on DNA repair capacity, or in the amount of membrane ion channel commonly used for cisplatin uptake. Also, we noted that glutathione intracellular levels, and expression and activity of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) were determinant for cisplatin cytotoxicity. Remarkably, analysis of gene expression in non-small cell lung cancer patients of the TCGA data bank revealed that there is a significant lower overall survival rate in the subset of patients bearing tumors with unbalanced levels of NRF2/KEAP1 and, as consequence, increased expression of NRF2 target genes. Thus, the results indicate that NRF2 and glutathione levels figure as important cisplatin resistance biomarkers in lung cancer.

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Section: Methodsmentioning

confidence: 99%

The balance between NRF2/GSH antioxidant mediated pathway and DNA repair modulates cisplatin resistance in lung cancer cells

Silva

Rocha

Kinker

et al. 2019

Sci Rep

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“…As cells from these patients are more sensitive to DNA damage, their use has been proposed to better understand the effects of UVA-light in human cells (Schuch et al, 2017). In fact, evidence that protein oxidation due to UVA-light may aggravate XP cells' phenotype has been obtained from NER and pol eta deficient cells (Cortat et al, 2013;Moreno et al, 2019a). Pol eta (XP-V) deficient cells are able to repair bulky DNA lesions such as CPDs induced by UVC light but have impaired NER when these lesions are induced by UVA light, probably due to protein oxidation.…”

Section: Dna Glycosylase Neil1 Binds and Excises Psoraleninduced Monomentioning

confidence: 99%

“…Pol eta (XP-V) deficient cells are able to repair bulky DNA lesions such as CPDs induced by UVC light but have impaired NER when these lesions are induced by UVA light, probably due to protein oxidation. The use of antioxidants protected UVA-irradiated cells, improved CPD removal, as well as the ability of these cells to replicate their damaged DNA (Moreno et al, 2019a). Moreover, the lack of pol eta and other TLS proteins has been reported to impair NER due to the recruitment of RPA to TLS site (Auclair et al, 2010;Tsaalbi-Shtylik et al, 2014), and the limiting effect of this protein may be even stronger in conditions of oxidative stress.…”

Section: Dna Glycosylase Neil1 Binds and Excises Psoraleninduced Monomentioning

confidence: 99%

Cooperation and interplay between base and nucleotide excision repair pathways: From DNA lesions to proteins

et al. 2020

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Base and nucleotide excision repair (BER and NER) pathways are normally associated with removal of specific types of DNA damage: small base modifications (such as those induced by DNA oxidation) and bulky DNA lesions (such as those induced by ultraviolet or chemical carcinogens), respectively. However, growing evidence indicates that this scenario is much more complex and these pathways exchange proteins and cooperate with each other in the repair of specific lesions. In this review, we highlight studies discussing the involvement of NER in the repair of DNA damage induced by oxidative stress, and BER participating in the removal of bulky adducts on DNA. Adding to this complexity, UVA light experiments revealed that oxidative stress also causes protein oxidation, directly affecting proteins involved in both NER and BER. This reduces the cell's ability to repair DNA damage with deleterious implications to the cells, such as mutagenesis and cell death, and to the organisms, such as cancer and aging. Finally, an interactome of NER and BER proteins is presented, showing the strong connection between these pathways, indicating that further investigation may reveal new functions shared by them, and their cooperation in maintaining genome stability.

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“…The NER and BER pathways are important to repair damage induced by ROS and present important connections and proteins that interact [10,107,108]. High levels of ROS, due to oxidative stress conditions, contribute to genomic instability and cause DNA damage such as SSBs and DSBs and also contribute to failures during DNA replication [109,110]. In order to protect against oxidative stress caused by high levels of ROS and return to equilibrium, cells have developed protection strategies, an example of which is the action of glutathione (GSH), one of the main antioxidant molecules, responsible for the elimination of ROS.…”

Section: Removing Single-strand Breaks and Base Damage By Base Excision Repair And Bulky Lesions By Nucleotide Excision Repairmentioning

confidence: 99%

Interface of DNA Repair and Metabolism

Marconi

Ranfley

Menck

et al. 2020

Curr. Tissue Microenviron. Rep.

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Purpose of Review DNA is naturally very unstable and several agents are capable of damaging and altering its structure, thus leading to several negative consequences. Therefore, this review seeks to better understand the relationship between different DNA repair mechanisms and metabolic pathways, and how such a relationship can influence the outcome of different human inflammatory diseases. Recent Findings Studies have shown that factors involved in DNA repair are also involved in the regulation of cellular metabolism in response to DNA damage. Indeed, it was demonstrated that cells deficient in DNA repair have abrupt rewiring of cell metabolism. Additionally, oxidative stress observed in several human disorders increase DNA damage that contributes in metabolic changes and diseases progression. Summary DNA molecule is daily exposed to several types of damages and, in mammal cells, the DNA damage response (DDR) is responsible to monitor and repair genotoxic stress. The activation of DDR mostly depends on the DNA damage type and involves the activation of sensors, transducers, and effector proteins. The effector protein pathways are closely linked to several cell biology processes, such as apoptosis, senescence, cell cycle control, inflammatory response, and gene transcriptions. Recently, it was demonstrated that DDR genes are involved in cell metabolism and contribute to DNA repair and cell survival. Understanding as DNA damage impacts in cell function is important to comprehend and treat several human inflammatory diseases.

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

Cited by 24 publications

References 67 publications

The balance between NRF2/GSH antioxidant mediated pathway and DNA repair modulates cisplatin resistance in lung cancer cells

The balance between NRF2/GSH antioxidant mediated pathway and DNA repair modulates cisplatin resistance in lung cancer cells

Cooperation and interplay between base and nucleotide excision repair pathways: From DNA lesions to proteins

Interface of DNA Repair and Metabolism

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