hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway
Paquet, Nicolas, Adams, Mark N., Leong, Vincent, Ashton, Nicholas W., Touma, Christine, Gamsjaeger, Roland, Cubeddu, Liza, Beard, Sam, Burgess, Joshua T., Bolderson, Emma, O'Byrne, Ken J., & Richard, Derek J. (2015) hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway. Nucleic Acids Research, 43(18), pp. 8817-8829.
The maintenance of genome stability is essential to prevent loss of genetic information and the development of diseases such as cancer. One of the most common forms of damage to the genetic code is the oxidation of DNA by reactive oxygen species (ROS), of which 8-oxo-7,8-dihydro-guanine (8-oxoG) is the most frequent modification. Previous studies have established that human single-stranded DNA-binding protein 1 (hSSB1) is essential for the repair of double-stranded DNA breaks by the process of homologous recombination. Here we show that hSSB1 is also required following oxidative damage. Cells lacking hSSB1 are sensitive to oxidizing agents, have deficient ATM and p53 activation and cannot effectively repair 8-oxoGs. Furthermore, we demonstrate that hSSB1 forms a complex with the human oxo-guanine glycosylase 1 (hOGG1) and is important for hOGG1 localization to the damaged chromatin. In vitro, hSSB1 binds directly to DNA containing 8-oxoguanines and enhances hOGG1 activity. These results underpin the crucial role hSSB1 plays as a guardian of the genome.
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|Item Type:||Journal Article|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2015 The Authors|
|Copyright Statement:||This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.|
|Deposited On:||16 Oct 2015 01:07|
|Last Modified:||19 Oct 2015 04:10|
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