The protein Xeroderma Pigmentosum C (XPC) is directly involved in Nucleotide Excision Repair (NER), a DNA repair mechanism through which bulky DNA adducts are removed. Experimental evidence suggest that XPC might be involved also in the control of oxidative DNA damage, whose major repair pathway is Base Excision Repair (BER). In the present study, the authors analyze the effects of XPC mutations in BER, by studying primary fibroblasts derived from patients affected by Xeroderma Pigmentosum type C. All the cell lines were characterized by altered mRNA expression of OGG1, MYH, APE1, LIG3, XRCC1 and Polβ, as well as by lower OGG1, MYH and APE1 protein levels. Higher load and persistence of DNA oxidative lesions were observed in patients’ fibroblasts, compared to cells derived from healthy donors. These results suggest that mutant forms of XPC can alter not only NER, but also BER, leading to enhanced oxidative DNA damage and, consequently, facilitating the insurgence of cancer not only in photo-exposed but also in photo-protected areas.

The protein Xeroderma Pigmentosum C (XPC) is directly involved in Nucleotide Excision Repair (NER), a DNA repair mechanism through which bulky DNA adducts are removed. Experimental evidence suggest that XPC might be involved also in the control of oxidative DNA damage, whose major repair pathway is Base Excision Repair (BER). In the present study, the authors analyze the effects of XPC mutations in BER, by studying primary fibroblasts derived from patients affected by Xeroderma Pigmentosum type C. All the cell lines were characterized by altered mRNA expression of OGG1, MYH, APE1, LIG3, XRCC1 and Polβ, as well as by lower OGG1, MYH and APE1 protein levels. Higher load and persistence of DNA oxidative lesions were observed in patients’ fibroblasts, compared to cells derived from healthy donors. These results suggest that mutant forms of XPC can alter not only NER, but also BER, leading to enhanced oxidative DNA damage and, consequently, facilitating the insurgence of cancer not only in photo-exposed but also in photo-protected areas.

Analysis of XPC mutants: effects on the base excision repair pathway and oxidative DNA damage

MARINELLO, FEDERICO
2021/2022

Abstract

The protein Xeroderma Pigmentosum C (XPC) is directly involved in Nucleotide Excision Repair (NER), a DNA repair mechanism through which bulky DNA adducts are removed. Experimental evidence suggest that XPC might be involved also in the control of oxidative DNA damage, whose major repair pathway is Base Excision Repair (BER). In the present study, the authors analyze the effects of XPC mutations in BER, by studying primary fibroblasts derived from patients affected by Xeroderma Pigmentosum type C. All the cell lines were characterized by altered mRNA expression of OGG1, MYH, APE1, LIG3, XRCC1 and Polβ, as well as by lower OGG1, MYH and APE1 protein levels. Higher load and persistence of DNA oxidative lesions were observed in patients’ fibroblasts, compared to cells derived from healthy donors. These results suggest that mutant forms of XPC can alter not only NER, but also BER, leading to enhanced oxidative DNA damage and, consequently, facilitating the insurgence of cancer not only in photo-exposed but also in photo-protected areas.
2021
Analysis of XPC mutants: effects on the base excision repair pathway and oxidative DNA damage
The protein Xeroderma Pigmentosum C (XPC) is directly involved in Nucleotide Excision Repair (NER), a DNA repair mechanism through which bulky DNA adducts are removed. Experimental evidence suggest that XPC might be involved also in the control of oxidative DNA damage, whose major repair pathway is Base Excision Repair (BER). In the present study, the authors analyze the effects of XPC mutations in BER, by studying primary fibroblasts derived from patients affected by Xeroderma Pigmentosum type C. All the cell lines were characterized by altered mRNA expression of OGG1, MYH, APE1, LIG3, XRCC1 and Polβ, as well as by lower OGG1, MYH and APE1 protein levels. Higher load and persistence of DNA oxidative lesions were observed in patients’ fibroblasts, compared to cells derived from healthy donors. These results suggest that mutant forms of XPC can alter not only NER, but also BER, leading to enhanced oxidative DNA damage and, consequently, facilitating the insurgence of cancer not only in photo-exposed but also in photo-protected areas.
XPC
base excision repair
oxidative DNA damage
File in questo prodotto:
File Dimensione Formato  
Marinello_Federico.pdf.pdf

accesso aperto

Dimensione 2.13 MB
Formato Adobe PDF
2.13 MB Adobe PDF Visualizza/Apri

The text of this website © Università degli studi di Padova. Full Text are published under a non-exclusive license. Metadata are under a CC0 License

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12608/34445