title: Understanding nucleotide excision repair and its roles in cancer and ageing.
abstract: Nucleotide excision repair (NER) eliminates various structurally unrelated DNA lesions by a multiwise 'cut and patch'-type reaction. The global genome NER (GG-NER) subpathway prevents mutagenesis by probing the genome for helix-distorting lesions, whereas transcription-coupled NER (TC-NER) removes transcription-blocking lesions to permit unperturbed gene expression, thereby preventing cell death. Consequently, defects in GG-NER result in cancer predisposition, whereas defects in TC-NER cause a variety of diseases ranging from ultraviolet radiation-sensitive syndrome to severe premature ageing conditions such as Cockayne syndrome. Recent studies have uncovered new aspects of DNA-damage detection by NER, how NER is regulated by extensive post-translational modifications, and the dynamic chromatin interactions that control its efficiency. Based on these findings, a mechanistic model is proposed that explains the complex genotype-phenotype correlations of transcription-coupled repair disorders.
authors: 1] Department of Genetics, Cancer Genomics Netherlands, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. [2].
authors: Jurgen A
authors: JA
authors: Marteijn
authors: 1] Department of Genetics, Cancer Genomics Netherlands, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. [2].
authors: Hannes
authors: H
authors: Lans
authors: Department of Genetics, Cancer Genomics Netherlands, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Wim
authors: W
authors: Vermeulen
authors: Department of Genetics, Cancer Genomics Netherlands, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Jan H J
authors: JH
authors: Hoeijmakers
mesh_terms: D000375:Aging / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics*; D025801:Ubiquitin / Q000502:physiology
chemical_list: D025801:Ubiquitin