hSSB1 (NABP2/ OBFC2B) is required for the repair of 8-oxo-guanine by the hOGG1-mediated base excision repair pathway.
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.
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia derek.richard@qut.edu.au.
Nicolas
N
Paquet
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia.
Mark N
MN
Adams
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia.
Vincent
V
Leong
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia.
Nicholas W
NW
Ashton
School of Science and Health, University of Western Sydney, Penrith, NSW 2751 Australia.
Christine
C
Touma
School of Science and Health, University of Western Sydney, Penrith, NSW 2751 Australia School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
Roland
R
Gamsjaeger
School of Science and Health, University of Western Sydney, Penrith, NSW 2751 Australia School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
Liza
L
Cubeddu
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia.
Sam
S
Beard
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia.
Joshua T
JT
Burgess
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia.
Emma
E
Bolderson
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia.
Ken J
KJ
O'Byrne
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia derek.richard@qut.edu.au.
Derek J
DJ
Richard
D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002470:Cell Survival; D002843:Chromatin / Q000201:enzymology / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress
D002843:Chromatin; D018736:DNA Adducts; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C504091:NABP2 protein, human; C024829:8-hydroxyguanine; D006147:Guanine; D064007:Ataxia Telangiectasia Mutated Proteins; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human