%0 Journal Article
%T Hydrogen peroxide induced genomic instability in nucleotide excision repair-deficient lymphoblastoid cells
%A Kalpana Gopalakrishnan
%A Grace Low
%A Aloysius Ting
%A Prarthana Srikanth
%A Predrag Slijepcevic
%A M Prakash Hande
%J Genome Integrity
%D 2010
%I BioMed Central
%R 10.1186/2041-9414-1-16
%X 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.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.The nucleotide excision repair (NER) pathway is a versatile DNA repair mechanism that recognizes and efficiently removes an array of structurally diverse DNA lesions including ultraviolet (UV)-induced lesions, intra-strand crosslinks and bulky chemical adducts such as those induced by compounds in tobacco smoke. The NER comprises of more than three dozen genes working in spatial and temporal concert and is differentiated into two sub-pathways - the global genome-NER (GG-NER) and transcription coupled repair (TCR) - that differ only in damage recognition [1,2].Inherited defects in the NER predispose an individual to genetic disorders featuring genomic instability and segmental progeria - Xeroderma pigmentosum (XP), Cockayne syndrome (CS) and Trichothiodystrophy (TTD). XP is a rare autosomal recessive congenital disorder that arises from mutations in XP proteins, XPA - XPG, and a variant form XPV. XP patients are predisposed to sun-induced cutaneous cancer incidence by more than a thousand-fold
%U http://www.genomeintegrity.com/content/1/1/16