Understanding nucleotide excision repair and its roles in cancer and ageing

Jurgen A. Marteijn, Hannes Lans, Wim Vermeulen, Jan H.J. Hoeijmakers

Research output: Contribution to journalReview articlepeer-review

868 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)465-481
Number of pages17
JournalNature Reviews Molecular Cell Biology
Volume15
Issue number7
DOIs
Publication statusPublished - Jul 2014
Externally publishedYes

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