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

19 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 number27466
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 8 Jun 2016

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