4.7 Article

hSSB1 (NABP2/OBFC2B) is regulated by oxidative stress

Journal

SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/srep27446

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Funding

  1. NHMRC project [1066550]
  2. ARC project [DP 120103099]
  3. Queensland Health Senior Clinical Research Fellowship
  4. NHMRC Early Career Fellowship [1091589]
  5. Marylyn Mayo scholarship by Cancer Council Queensland
  6. UWS Women's Research Fellowship
  7. National Health and Medical Research Council of Australia [1091589, 1066550] Funding Source: NHMRC

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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.

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