{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T13:27:15Z","timestamp":1776259635570,"version":"3.50.1"},"reference-count":57,"publisher":"ScienceOpen","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>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 (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Loss of functional XPB or XPD but not XPA led to enhanced sensitivity towards H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced cell death. XP-deficient lymphoblastoid cells exhibited increased susceptibility to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-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 H<jats:sub>2<\/jats:sub>O<jats:sub>2 <\/jats:sub>treatment.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Taken together, our data implicate a role for the NER in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-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 H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/2041-9414-1-16","type":"journal-article","created":{"date-parts":[[2011,1,5]],"date-time":"2011-01-05T19:37:14Z","timestamp":1294256234000},"source":"Crossref","is-referenced-by-count":22,"title":["Hydrogen peroxide induced genomic instability in nucleotide excision repair-deficient lymphoblastoid cells"],"prefix":"10.14293","volume":"1","author":[{"given":"Kalpana","family":"Gopalakrishnan","sequence":"first","affiliation":[{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace Kah Mun","family":"Low","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aloysius Poh Leong","family":"Ting","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prarthana","family":"Srikanth","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Predrag","family":"Slijepcevic","sequence":"additional","affiliation":[{"name":"Division of Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge UB8 3PH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Prakash","family":"Hande","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5403","published-online":{"date-parts":[[2010]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/35077232","article-title":"Genome maintenance mechanisms for preventing cancer","volume":"411","author":"JH Hoeijmakers","year":"2001","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1146\/annurev.bi.65.070196.000355","article-title":"DNA excision repair","volume":"65","author":"A Sancar","year":"1996","journal-title":"Annu Rev Biochem"},{"key":"B3","first-page":"4","article-title":"Xeroderma pigmentosum","volume":"13","author":"J Norgauer","year":"2003","journal-title":"Eur J Dermatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/S1357-4310(98)01394-X","article-title":"Xeroderma pigmentosum and the role of UV-induced DNA damage in skin cancer","volume":"5","author":"H van Steeg","year":"1999","journal-title":"Mol Med Today"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3554","DOI":"10.1093\/emboj\/20.13.3554","article-title":"Double-check probing of DNA bending and unwinding by XPA-RPA: an architectural function in DNA repair","volume":"20","author":"M Missura","year":"2001","journal-title":"EMBO J"},{"key":"B6","doi-asserted-by":"publisher","first-page":"23465","DOI":"10.1074\/jbc.272.38.23465","article-title":"Nucleotide excision repair in mammalian cells","volume":"272","author":"RD Wood","year":"1997","journal-title":"J Biol Chem"},{"key":"B7","doi-asserted-by":"publisher","first-page":"4258","DOI":"10.1074\/jbc.275.6.4258","article-title":"TFIIH with inactive XPD helicase functions in transcription initiation but is defective in DNA repair","volume":"275","author":"GS Winkler","year":"2000","journal-title":"J Biol Chem"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.neuroscience.2006.12.020","article-title":"Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship","volume":"145","author":"KH Kraemer","year":"2007","journal-title":"Neuroscience"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1002\/humu.20392","article-title":"Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome","volume":"27","author":"KS Oh","year":"2006","journal-title":"Hum Mutat"},{"key":"B10","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1002\/(SICI)1098-1004(1998)12:2<103::AID-HUMU5>3.0.CO;2-6","article-title":"Distribution of mutations in the human xeroderma pigmentosum group A gene and their relationships to the functional regions of the DNA damage recognition protein","volume":"12","author":"JC States","year":"1998","journal-title":"Hum Mutat"},{"key":"B11","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1101\/gad.13.7.768","article-title":"Molecular mechanism of nucleotide excision repair","volume":"13","author":"WL de Laat","year":"1999","journal-title":"Genes Dev"},{"key":"B12","volume-title":"DNA Repair and Mutagenesis","author":"EC Friedberg","year":"1995"},{"key":"B13","first-page":"389","article-title":"Involvement of the nucleotide excision repair proteins in the removal of oxidative DNA base damage in mammalian cells","volume":"50","author":"I Rybanska","year":"2003","journal-title":"Neoplasma"},{"key":"B14","first-page":"1899s","article-title":"Enzymatic repair of oxidative DNA damage","volume":"54","author":"MS Satoh","year":"1994","journal-title":"Cancer Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s00204-008-0304-z","article-title":"Intracellular redox status and oxidative stress: implications for cell proliferation, apoptosis, and carcinogenesis","volume":"82","author":"JM Mates","year":"2008","journal-title":"Arch Toxicol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1002\/iub.61","article-title":"Molecular mechanisms of oxidative stress-induced carcinogenesis: from epidemiology to oxygenomics","volume":"60","author":"S Toyokuni","year":"2008","journal-title":"IUBMB Life"},{"key":"B17","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/35041687","article-title":"Oxidants, oxidative stress and the biology of ageing","volume":"408","author":"T Finkel","year":"2000","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","first-page":"22355","DOI":"10.1074\/jbc.M002259200","article-title":"The oxidative DNA lesion 8,5'-(S)-cyclo-2'-deoxyadenosine is repaired by the nucleotide excision repair pathway and blocks gene expression in mammalian cells","volume":"275","author":"PJ Brooks","year":"2000","journal-title":"J Biol Chem"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3832","DOI":"10.1073\/pnas.070471597","article-title":"Removal of oxygen free-radical-induced 5',8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells","volume":"97","author":"I Kuraoka","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"B20","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1212\/WNL.55.10.1442","article-title":"Cockayne syndrome and xeroderma pigmentosum","volume":"55","author":"I Rapin","year":"2000","journal-title":"Neurology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ccr.2006.05.027","article-title":"An Xpd mouse model for the combined xeroderma pigmentosum\/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria","volume":"10","author":"JO Andressoo","year":"2006","journal-title":"Cancer Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1016\/j.biocel.2008.05.009","article-title":"Oxidative damage induced genotoxic effects in human fibroblasts from Xeroderma Pigmentosum group A patients","volume":"40","author":"GK Low","year":"2008","journal-title":"Int J Biochem Cell Biol"},{"issue":"1-2","key":"B23","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1111\/j.1582-4934.2009.00945.x","article-title":"Telomere attrition and genomic instability in xeroderma pigmentosum type-B deficient fibroblasts under oxidative stress","volume":"14","author":"AP Ting","year":"2010","journal-title":"J Cell Mol Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.toxlet.2003.10.020","article-title":"Synergistic DNA damage by oxidative stress (induced by H2O2) and nongenotoxic environmental chemicals in human fibroblasts","volume":"147","author":"A Lueken","year":"2004","journal-title":"Toxicol Lett"},{"key":"B25","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1080\/095530096144842","article-title":"Induction and persistence of cytogenetic damage in mouse splenocytes following whole-body X-irradiation analysed by fluorescence in situ hybridization. II. Micronuclei","volume":"70","author":"MP Hande","year":"1996","journal-title":"Int J Radiat Biol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1002\/jcp.21276","article-title":"Short dysfunctional telomeres impair the repair of arsenite-induced oxidative damage in mouse cells","volume":"214","author":"JP Newman","year":"2008","journal-title":"J Cell Physiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1083\/jcb.144.4.589","article-title":"Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice","volume":"144","author":"MP Hande","year":"1999","journal-title":"J Cell Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1385\/MB:26:3:249","article-title":"The comet assay for DNA damage and repair: principles, applications, and limitations","volume":"26","author":"AR Collins","year":"2004","journal-title":"Mol Biotechnol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.bios.2009.06.035","article-title":"Electrochemical detection of natural DNA damage induced by ferritin\/ascorbic acid\/H2O2 system and amplification of DNA damage by endonuclease Fpg","volume":"25","author":"Y Liu","year":"2009","journal-title":"Biosens Bioelectron"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1016\/S0891-5849(00)00224-0","article-title":"Oxidative stress and cell cycle checkpoint function","volume":"28","author":"RE Shackelford","year":"2000","journal-title":"Free Radic Biol Med"},{"key":"B31","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1080\/07391102.1995.10508867","article-title":"Calculation of hydroxyl radical attack on different forms of DNA","volume":"13","author":"V Michalik","year":"1995","journal-title":"J Biomol Struct Dyn"},{"key":"B32","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S1097-2765(00)80172-0","article-title":"Base excision repair of oxidative DNA damage activated by XPG protein","volume":"3","author":"A Klungland","year":"1999","journal-title":"Mol Cell"},{"key":"B33","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1093\/emboj\/cdg016","article-title":"Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase","volume":"22","author":"Y Shimizu","year":"2003","journal-title":"EMBO J"},{"key":"B34","doi-asserted-by":"publisher","first-page":"24213","DOI":"10.1074\/jbc.M109.000745","article-title":"Checkpoint kinase ATR promotes nucleotide excision repair of UV-induced DNA damage via physical interaction with xeroderma pigmentosum group A","volume":"284","author":"SM Shell","year":"2009","journal-title":"J Biol Chem"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1158\/0008-5472.CAN-05-3403","article-title":"Phosphorylation of nucleotide excision repair factor xeroderma pigmentosum group A by ataxia telangiectasia mutated and Rad3-related-dependent checkpoint pathway promotes cell survival in response to UV irradiation","volume":"66","author":"X Wu","year":"2006","journal-title":"Cancer Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1126\/science.8465201","article-title":"DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor","volume":"260","author":"L Schaeffer","year":"1993","journal-title":"Science"},{"key":"B37","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1002\/j.1460-2075.1994.tb06522.x","article-title":"The ERCC2\/DNA repair protein is associated with the class II BTF2\/TFIIH transcription factor","volume":"13","author":"L Schaeffer","year":"1994","journal-title":"EMBO J"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1128\/MCB.01229-08","article-title":"An Xpb mouse model for combined xeroderma pigmentosum and cockayne syndrome reveals progeroid features upon further attenuation of DNA repair","volume":"29","author":"JO Andressoo","year":"2009","journal-title":"Mol Cell Biol"},{"key":"B39","first-page":"89","article-title":"Disruption of the mouse xeroderma pigmentosum group D DNA repair\/basal transcription gene results in preimplantation lethality","volume":"58","author":"J de Boer","year":"1998","journal-title":"Cancer Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1016\/j.dnarep.2008.06.009","article-title":"Cell-type-specific consequences of nucleotide excision repair deficiencies: Embryonic stem cells versus fibroblasts","volume":"7","author":"WH de","year":"2008","journal-title":"DNA Repair (Amst)"},{"key":"B41","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1093\/toxsci\/kfq113","article-title":"XPC silencing sensitizes glioma cells to arsenic trioxide via increased oxidative damage","volume":"116","author":"SY Liu","year":"2010","journal-title":"Toxicol Sci"},{"key":"B42","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1093\/mutage\/gep059","article-title":"Newly identified CHO ERCC3\/XPB mutations and phenotype characterization","volume":"25","author":"I Rybanska","year":"2010","journal-title":"Mutagenesis"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/ng1633","article-title":"XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer","volume":"37","author":"P Munoz","year":"2005","journal-title":"Nat Genet"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1126\/science.1103619","article-title":"Defective telomere lagging strand synthesis in cells lacking WRN helicase activity","volume":"306","author":"L Crabbe","year":"2004","journal-title":"Science"},{"key":"B45","doi-asserted-by":"publisher","first-page":"8437","DOI":"10.1128\/MCB.24.19.8437-8446.2004","article-title":"Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes","volume":"24","author":"X Du","year":"2004","journal-title":"Mol Cell Biol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"41110","DOI":"10.1074\/jbc.M205396200","article-title":"Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases","volume":"277","author":"PL Opresko","year":"2002","journal-title":"J Biol Chem"},{"key":"B47","doi-asserted-by":"publisher","first-page":"32069","DOI":"10.1074\/jbc.M505211200","article-title":"POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates","volume":"280","author":"PL Opresko","year":"2005","journal-title":"J Biol Chem"},{"key":"B48","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1098\/rstb.1995.0013","article-title":"On the regulation of the p53 tumour suppressor, and its role in the cellular response to DNA damage","volume":"347","author":"DP Lane","year":"1995","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1126\/science.281.5383.1674","article-title":"Enhanced phosphorylation of p53 by ATM in response to DNA damage","volume":"281","author":"S Banin","year":"1998","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1177\/154411130201300603","article-title":"P21Waf1 control of epithelial cell cycle and cell fate","volume":"13","author":"WC Weinberg","year":"2002","journal-title":"Crit Rev Oral Biol Med"},{"key":"B51","doi-asserted-by":"publisher","first-page":"250","DOI":"10.2174\/138920209788488544","article-title":"Involvement of nucleotide excision and mismatch repair mechanisms in double strand break repair","volume":"10","author":"Y Zhang","year":"2009","journal-title":"Curr Genomics"},{"key":"B52","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4161\/cc.3.2.658","article-title":"Role of p21WAF1 in the cellular response to UV","volume":"3","author":"R Fotedar","year":"2004","journal-title":"Cell Cycle"},{"key":"B53","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.1038\/sj.onc.1209315","article-title":"P21Cip1\/WAF1 downregulation is required for efficient PCNA ubiquitination after UV irradiation","volume":"25","author":"G Soria","year":"2006","journal-title":"Oncogene"},{"key":"B54","doi-asserted-by":"publisher","first-page":"5000","DOI":"10.1158\/1078-0432.CCR-08-0746","article-title":"Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics","volume":"14","author":"AC Mita","year":"2008","journal-title":"Clin Cancer Res"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1016\/j.dnarep.2004.05.005","article-title":"Mechanisms of DNA damage recognition and strand discrimination in human nucleotide excision repair","volume":"3","author":"R Dip","year":"2004","journal-title":"DNA Repair (Amst)"},{"key":"B56","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S0300-9084(99)80036-4","article-title":"DNA damage recognition during nucleotide excision repair in mammalian cells","volume":"81","author":"RD Wood","year":"1999","journal-title":"Biochimie"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1016\/j.biocel.2005.01.010","article-title":"Irreversible cellular senescence induced by prolonged exposure to H2O2 involves DNA-damage-and-repair genes and telomere shortening","volume":"37","author":"J Duan","year":"2005","journal-title":"Int J Biochem Cell Biol"}],"container-title":["Genome Integrity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/scienceopen.com\/document_file\/74be5489-dfa1-4629-a1bc-c6a6a66ffdfc\/ScienceOpen\/74be5489-dfa1-4629-a1bc-c6a6a66ffdfc.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/scienceopen.com\/hosted-document?doi=10.1186\/2041-9414-1-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T11:26:55Z","timestamp":1694777215000},"score":1,"resource":{"primary":{"URL":"https:\/\/scienceopen.com\/hosted-document?doi=10.1186\/2041-9414-1-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010]]},"references-count":57,"URL":"https:\/\/doi.org\/10.1186\/2041-9414-1-16","relation":{},"ISSN":["2041-9414"],"issn-type":[{"value":"2041-9414","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010]]},"published":{"date-parts":[[2010]]}}}