Please use this identifier to cite or link to this item: https://doi.org/10.1186/2041-9414-1-16
Title: Hydrogen peroxide induced genomic instability in nucleotide excision repair-deficient lymphoblastoid cells
Authors: Gopalakrishnan, K
Low, G.K.M 
Ting, A.P.L
Srikanth, P 
Slijepcevic, P
Hande, M.P 
Keywords: nucleic acid binding protein
unclassified drug
xeroderma pigmentosum group A protein
xeroderma pigmentosum group B protein
xeroderma pigmentosum group D protein
apoptosis
article
cell cycle G2 phase
cell cycle M phase
cell population
cell viability
controlled study
DNA damage
excision repair
genomic instability
human
human cell
lymphoblastoid cell
oxidative stress
priority journal
protein function
telomere
Issue Date: 2010
Citation: Gopalakrishnan, K, Low, G.K.M, Ting, A.P.L, Srikanth, P, Slijepcevic, P, Hande, M.P (2010). Hydrogen peroxide induced genomic instability in nucleotide excision repair-deficient lymphoblastoid cells. Genome Integrity 1 : 16. ScholarBank@NUS Repository. https://doi.org/10.1186/2041-9414-1-16
Abstract: Background: The Nucleotide Excision Repair (NER) pathway specialises in UV-induced DNA damage repair. Inherited defects in the NER can predispose individuals to Xeroderma Pigmentosum (XP). UV-induced DNA damage cannot account for the manifestation of XP in organ systems not directly exposed to sunlight. While the NER has recently been implicated in the repair of oxidative DNA lesions, it is not well characterised. Therefore we sought to investigate the role of NER factors Xeroderma Pigmentosum A (XPA), XPB and XPD in oxidative DNA damage-repair by subjecting lymphoblastoid cells from patients suffering from XP-A, XP-D and XP-B with Cockayne Syndrome to hydrogen peroxide (H2O2).Results: Loss of functional XPB or XPD but not XPA led to enhanced sensitivity towards H2O2-induced cell death. XP-deficient lymphoblastoid cells exhibited increased susceptibility to H2O2-induced DNA damage with XPD showing the highest susceptibility and lowest repair capacity. Furthermore, XPB- and XPD-deficient lymphoblastoid cells displayed enhanced DNA damage at the telomeres. XPA- and XPB-deficient lymphoblastoid cells also showed differential regulation of XPD following H2O2treatment.Conclusions: Taken together, our data implicate a role for the NER in H2O2-induced oxidative stress management and further corroborates that oxidative stress is a significant contributing factor in XP symptoms. Resistance of XPA-deficient lymphoblastoid cells to H2O2-induced cell death while harbouring DNA damage poses a potential cancer risk factor for XPA patients. Our data implicate XPB and XPD in the protection against oxidative stress-induced DNA damage and telomere shortening, and thus premature senescence. © 2010 Gopalakrishnan et al; licensee BioMed Central Ltd.
Source Title: Genome Integrity
URI: https://scholarbank.nus.edu.sg/handle/10635/175001
ISSN: 20419414
DOI: 10.1186/2041-9414-1-16
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