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Antioxid Redox Signal. 2013 Jun 20;18(18):2409-19. doi: 10.1089/ars.2012.5036. Epub 2012 Dec 7.

Oxidative DNA damage and nucleotide excision repair.

Author information

1
Leiden University Medical Center, Department of Toxicogenetics, Leiden, The Netherlands.

Abstract

SIGNIFICANCE:

Oxidative DNA damage is repaired by multiple, overlapping DNA repair pathways. Accumulating evidence supports the hypothesis that nucleotide excision repair (NER), besides base excision repair (BER), is also involved in neutralizing oxidative DNA damage.

RECENT ADVANCES:

NER includes two distinct sub-pathways: transcription-coupled NER (TC-NER) and global genome repair (GG-NER). The CSA and CSB proteins initiate the onset of TC-NER. Recent findings show that not only CSB, but also CSA is involved in the repair of oxidative DNA lesions, in the nucleus as well as in mitochondria. The XPG protein is also of importance for the removal of oxidative DNA lesions, as it may enhance the initial step of BER. Substantial evidence exists that support a role for XPC in NER and BER. XPC deficiency not only results in decreased repair of oxidative lesions, but has also been linked to disturbed redox homeostasis.

CRITICAL ISSUES:

The role of NER proteins in the regulation of the cellular response to oxidative (mitochondrial and nuclear) DNA damage may be the underlying mechanism of the pathology of accelerated aging in Cockayne syndrome patients, a driving force for internal cancer development in XP-A and XP-C patients, and a contributor to the mixed exhibited phenotypes of XP-G patients.

FUTURE DIRECTIONS:

Accumulating evidence indicates that DNA repair factors can be involved in multiple DNA repair pathways. However, the distinct detailed mechanism and consequences of these additional functions remain to be elucidated and can possibly shine a light on clinically related issues.

PMID:
23216312
PMCID:
PMC3671630
DOI:
10.1089/ars.2012.5036
[Indexed for MEDLINE]
Free PMC Article

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