hSSB1 (NABP2/OBFC2B) is regulated by oxidative stress

Nicolas Paquet, Mark N. Adams, Nicholas W. Ashton, Christine Touma, Roland Gamsjaeger, Liza Cubeddu, Vincent Leong, Sam Beard, Emma Bolderson, Catherine H. Botting, Kenneth J. O’Byrne, Derek J. Richard

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

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.
Original languageEnglish
Article number27446
Number of pages13
JournalScientific Reports
Volume6
Publication statusPublished - 8 Jun 2016

Keywords

  • DNA damage
  • diseases
  • genomes
  • nucleic acids
  • oxidative stress

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