Hydrogen peroxide induced genomic instability in nucleotide excision repair-deficient lymphoblastoid cells

Copyright @ 2010 Gopalakrishnan et al; licensee BioMed Central Ltd.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 H2O2 treatment. 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.This research is supported by the Defence Innovative Research Programme, Defence Science and Technology Agency, Singapore (POD: 0613592) and the Academic Research Fund, Ministry of Education, Singapore (T206B3108). Supported in part by a grant from British Council, PMI2 Connect (Grant Number: RC134)

Homoleptic ruthenium(III) chalcogenolates: A single precursor to metal chalcogenide nanoparticles catalyst

Eight homoleptic metal(III) arylchalcogenolate polymers [M(EPh-p-X) 3] n (M = Ru, Cr, and Mo) were characterized by PXRD. Structural solution of [Ru(SPh-p-tBu) 3] n1 was achieved by Rietveld refinement of the PXRD data. Pyrolysis of [Ru(SePh) 3] n4 produced nanostructured RuSe 2, which selectively catalyzed the reduction of nitro compounds in the presence of other functionalities. © 2011 The Royal Society of Chemistry.link_to_subscribed_fulltex

Biomarkers of ionizing radiation exposure: A multiparametric approach

10.4103/2041-9414.198911Genome Integrity816