PMID:17611195
| Citation |
Das, A, Boldogh, I, Lee, JW, Harrigan, JA, Hegde, ML, Piotrowski, J, de Souza Pinto, N, Ramos, W, Greenberg, MM, Hazra, TK, Mitra, S and Bohr, VA (2007) The human Werner syndrome protein stimulates repair of oxidative DNA base damage by the DNA glycosylase NEIL1. J. Biol. Chem. 282:26591-602 |
|---|---|
| Abstract |
The mammalian DNA glycosylase, NEIL1, specific for repair of oxidatively damaged bases in the genome via the base excision repair pathway, is activated by reactive oxygen species and prevents toxicity due to radiation. We show here that the Werner syndrome protein (WRN), a member of the RecQ family of DNA helicases, associates with NEIL1 in the early damage-sensing step of base excision repair. WRN stimulates NEIL1 in excision of oxidative lesions from bubble DNA substrates. The binary interaction between NEIL1 and WRN (K(D) = 60 nM) involves C-terminal residues 288-349 of NEIL1 and the RecQ C-terminal (RQC) region of WRN, and is independent of the helicase activity WRN. Exposure to oxidative stress enhances the NEIL-WRN association concomitant with their strong nuclear co-localization. WRN-depleted cells accumulate some prototypical oxidized bases (e.g. 8-oxoguanine, FapyG, and FapyA) indicating a physiological function of WRN in oxidative damage repair in mammalian genomes. Interestingly, WRN deficiency does not have an additive effect on in vivo damage accumulation in NEIL1 knockdown cells suggesting that WRN participates in the same repair pathway as NEIL1. |
| Links |
PubMed Online version:10.1074/jbc.M703343200 |
| Keywords |
Cell Line, Tumor; DNA Damage/physiology; DNA Damage/radiation effects; DNA Glycosylases/chemistry; DNA Glycosylases/genetics; DNA Glycosylases/metabolism; DNA Repair/physiology; DNA Repair/radiation effects; Exodeoxyribonucleases; Genome, Human/physiology; Humans; Oxidation-Reduction/radiation effects; Oxidative Stress/physiology; Oxidative Stress/radiation effects; Protein Binding/physiology; Protein Binding/radiation effects; Protein Structure, Tertiary/physiology; Pyrimidines/chemistry; Pyrimidines/metabolism; Reactive Oxygen Species/chemistry; Reactive Oxygen Species/metabolism; RecQ Helicases/chemistry; RecQ Helicases/genetics; RecQ Helicases/metabolism; Substrate Specificity/physiology; Substrate Specificity/radiation effects |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
References
See Help:References for how to manage references in EcoliWiki.