TY - JOUR
T1 - Understanding nucleotide excision repair and its roles in cancer and ageing
AU - Marteijn, Jurgen A.
AU - Lans, Hannes
AU - Vermeulen, Wim
AU - Hoeijmakers, Jan H.J.
N1 - Funding Information:
The authors acknowledge financial support from: the European commission FP7-Health-2008-200880, HEALTH-F2-2010-259893; US National Institutes of Health and National Institute on Ageing (1PO1 AG-17242-02), US National Institute of Environmental Health Sciences (NIEHS) (1UO1 ES011044); the Royal Academy of Arts and Sciences of the Netherlands (academic professorship awarded to J.H.J.H.); European Research Council Advanced Grants to J.H.J.H. and W.V.; a Koningin Wilhelmina Onderzoeksprijs (KWO) grant from the Dutch Cancer Society; Horizon Zenith project funding from the National Genomics Initiative; Earth and Life Sciences TOP grant to J.H.J.H. and Medical Sciences TOP grant to W.V., by the Dutch Science Organization (NWO); and an Erasmus MC fellowship to J.A.M.
PY - 2014/7
Y1 - 2014/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84904642416&partnerID=8YFLogxK
U2 - 10.1038/nrm3822
DO - 10.1038/nrm3822
M3 - Review article
C2 - 24954209
AN - SCOPUS:84904642416
SN - 1471-0072
VL - 15
SP - 465
EP - 481
JO - Nature Reviews Molecular Cell Biology
JF - Nature Reviews Molecular Cell Biology
IS - 7
ER -