4.1 Article

Role of Xeroderma pigmentosum D (XPD) protein in genome maintenance in human cells under oxidative stress

Publisher

ELSEVIER
DOI: 10.1016/j.mrgentox.2022.503444

Keywords

Xeroderma pigmentosum D; Nucleotide excision repair; Oxidative DNA damage; Genome instability; Telomeres

Funding

  1. Academic Research Fund, National University of Singapore

Ask authors/readers for more resources

The Xeroderma Pigmentosum D (XPD) protein plays a crucial role in the repair of oxidative DNA damage and telomere maintenance. Primary fibroblasts derived from patients with Xeroderma Pigmentosum D showed increased susceptibility, reduced repair capacity, and telomeric loss when exposed to oxidative stress. Gene expression profiling revealed alterations in genes involved in transcription, nucleotide metabolism, and cellular processes.
Xeroderma pigmentosum D (XPD) protein plays a pivotal role in the nucleotide excision repair pathway. XPD unwinds the local area of the damaged DNA by virtue of constituting transcription factor II H (TFIIH) and is important not only for repair but also for basal transcription. Although cells deficient in XPD have shown to be defective in oxidative base-lesion repair, the effects of the oxidative assault on primary fibroblasts from patients suffering from Xeroderma Pigmentosum D have not been fully explored. Therefore, we sought to investigate the role of XPD in oxidative DNA damage-repair by treating primary fibroblasts derived from a patient suffering from Xeroderma Pigmentosum D, with hydrogen peroxide. Our results show dose-dependent increase in genotoxicity with minimal effect on cytotoxicity with H2O2 in XPD deficient cells compared to control cells. XPD deficient cells displayed increased susceptibility and reduced repair capacity when subjected to DNA damage induced by oxidative stress. XPD deficient fibroblasts exhibited increased telomeric loss after H2O2 treatment. In addition, we demonstrated that chronic oxidative stress induced accelerated premature senescence characteristics. Gene expression profiling revealed alterations in genes involved in transcription and nucleotide metabolisms, as well as in cellular and cell cycle processes in a more significant way than in other pathways. This study highlights the role of XPD in the repair of oxidative stress and telomere maintenance. Lack of functional XPD seems to increase the susceptibility of oxidative stress-induced genotoxicity while retaining cell viability posing as a potential cancer risk factor of Xeroderma Pigmentosum D patients.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.1
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available