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Exp Cell Res. 2014 Nov 15;329(1):116-23. doi: 10.1016/j.yexcr.2014.08.010. Epub 2014 Aug 13.

Insight in the multilevel regulation of NER.

Author information

1
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
2
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: l.mullenders@lumc.nl.

Abstract

Nucleotide excision repair (NER) is a key component of the DNA damage response (DDR) and it is essential to safeguard genome integrity against genotoxic insults. The regulation of NER is primarily mediated by protein post-translational modifications (PTMs). The NER machinery removes a wide spectrum of DNA helix distorting lesions, including those induced by solar radiation, through two sub-pathways: global genome nucleotide excision repair (GG-NER) and transcription coupled nucleotide excision repair (TC-NER). Severe clinical consequences associated with inherited NER defects, including premature ageing, neurodegeneration and extreme cancer-susceptibility, underscore the biological relevance of NER. In the last two decades most of the core NER machinery has been elaborately described, shifting attention to molecular mechanisms that either facilitate NER in the context of chromatin or promote the timely and accurate interplay between NER factors and various post-translational modifications. In this review, we summarize and discuss the latest findings in NER. In particular, we focus on emerging factors and novel molecular mechanisms by which NER is regulated.

KEYWORDS:

DNA damage response; Global genome nucleotide excision repair; Nucleotide excision repair; Post-translational modifications; Transcription coupled nucleotide excision repair

PMID:
25128816
DOI:
10.1016/j.yexcr.2014.08.010
[Indexed for MEDLINE]

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