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Nat Rev Mol Cell Biol. 2014 Jul;15(7):465-81. doi: 10.1038/nrm3822.

Understanding nucleotide excision repair and its roles in cancer and ageing.

Author information

1
1] Department of Genetics, Cancer Genomics Netherlands, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. [2].
2
Department of Genetics, Cancer Genomics Netherlands, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.

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.

PMID:
24954209
DOI:
10.1038/nrm3822
[Indexed for MEDLINE]

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