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hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway

Authors :
Paquet, Nicolas
Adams, Mark
Leong, Vincent
Ashton, Nicholas
Touma, Christine
Gamsjaeger, Roland
Cubeddu, Liza
Beard, Samuel
Burgess, Joshua
Bolderson, Emma
O'Byrne, Ken
Richard, Derek
Paquet, Nicolas
Adams, Mark
Leong, Vincent
Ashton, Nicholas
Touma, Christine
Gamsjaeger, Roland
Cubeddu, Liza
Beard, Samuel
Burgess, Joshua
Bolderson, Emma
O'Byrne, Ken
Richard, Derek
Source :
Nucleic Acids Research
Publication Year :
2015

Abstract

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.

Details

Database :
OAIster
Journal :
Nucleic Acids Research
Notes :
application/pdf
Publication Type :
Electronic Resource
Accession number :
edsoai.ocn931767865
Document Type :
Electronic Resource