hSSB1 (NABP2/OBFC2B) is regulated by oxidative stress.
The maintenance of genome stability is an essential cellular process to prevent the development of diseases including cancer. hSSB1 (NABP2/ OBFC2A) is a critical component of the DNA damage response where it participates in the repair of double-strand DNA breaks and in base excision repair of oxidized guanine residues (8-oxoguanine) by aiding the localization of the human 8-oxoguanine glycosylase (hOGG1) to damaged DNA. Here we demonstrate that following oxidative stress, hSSB1 is stabilized as an oligomer which is required for hSSB1 to function in the removal of 8-oxoguanine. Monomeric hSSB1 shows a decreased affinity for oxidized DNA resulting in a cellular 8-oxoguanine-repair defect and in the absence of ATM signaling initiation. While hSSB1 oligomerization is important for the removal of 8-oxoguanine from the genome, it is not required for the repair of double-strand DNA-breaks by homologous recombination. These findings demonstrate a novel hSSB1 regulatory mechanism for the repair of damaged DNA.
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD4 102, Australia.
Nicolas
N
Paquet
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD4 102, 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, QLD4 102, Australia.
Nicholas W
NW
Ashton
School of Science and Health, Western Sydney University, Penrith, NSW 2751, Australia.
Christine
C
Touma
School of Science and Health, Western Sydney University, Penrith, NSW 2751, Australia.|School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
Roland
R
Gamsjaeger
School of Science and Health, Western Sydney University, 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, QLD4 102, Australia.
Vincent
V
Leong
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD4 102, Australia.
Sam
S
Beard
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD4 102, Australia.
Emma
E
Bolderson
Biomedical Sciences Research Complex, University of St Andrews, UK.
Catherine H
CH
Botting
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD4 102, Australia.
Kenneth J
KJ
O'Byrne
School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD4 102, Australia.
Derek J
DJ
Richard
D000595:Amino Acid Sequence; D001704:Biopolymers / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D018384:Oxidative Stress; D017386:Sequence Homology, Amino Acid
D001704:Biopolymers; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C504091:NABP2 protein, human