title: Oxidative DNA damage and nucleotide excision repair.
abstract: CONCLUSIONS
  Oxidative DNA damage is repaired by multiple, overlapping DNA repair pathways. Accumulating evidence supports the hypothesis that nucleotide excision repair (NER), besides base excision repair (BER), is also involved in neutralizing oxidative DNA damage.
  
  
  BACKGROUND
  NER includes two distinct sub-pathways: transcription-coupled NER (TC-NER) and global genome repair (GG-NER). The CSA and CSB proteins initiate the onset of TC-NER. Recent findings show that not only CSB, but also CSA is involved in the repair of oxidative DNA lesions, in the nucleus as well as in mitochondria. The XPG protein is also of importance for the removal of oxidative DNA lesions, as it may enhance the initial step of BER. Substantial evidence exists that support a role for XPC in NER and BER. XPC deficiency not only results in decreased repair of oxidative lesions, but has also been linked to disturbed redox homeostasis.
  
  
  RESULTS
  The role of NER proteins in the regulation of the cellular response to oxidative (mitochondrial and nuclear) DNA damage may be the underlying mechanism of the pathology of accelerated aging in Cockayne syndrome patients, a driving force for internal cancer development in XP-A and XP-C patients, and a contributor to the mixed exhibited phenotypes of XP-G patients.
  
  
  CONCLUSIONS
  Accumulating evidence indicates that DNA repair factors can be involved in multiple DNA repair pathways. However, the distinct detailed mechanism and consequences of these additional functions remain to be elucidated and can possibly shine a light on clinically related issues.
authors.affiliation: Leiden University Medical Center, Department of Toxicogenetics, Leiden, The Netherlands.
authors.forename: Joost P M
authors.initials: JP
authors.lastname: Melis
authors.forename: Harry
authors.initials: H
authors.lastname: van Steeg
authors.forename: Mirjam
authors.initials: M
authors.lastname: Luijten
mesh_terms: D000818:Animals; D003057:Cockayne Syndrome / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D010084:Oxidation-Reduction; D014158:Transcription, Genetic; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000378:metabolism; D051760:Xeroderma Pigmentosum Group A Protein / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C086984:XPC protein, human