hSSB1 is involved in the cellular response to oxidative DNA damage  — ASN Events
  1. Schedule
  2. Session Ten - Poster Session C including Refreshments
  3. hSSB1 is involved in the cellular response to oxidative DNA damage 

hSSB1 is involved in the cellular response to oxidative DNA damage  (#340)

Christine Touma 1 , Nicolas Paquet 2 , Roland Gamsjaeger 1 3 , Liza Cubeddu 1 3
  1. University of Western Sydney, Campbelltown, NSW, Australia
  2. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
  3. School of Molecular Bioscience , University of Sydney , Sydney , NSW, Australia

DNA in cells is subjected to high rates of oxidative damage by reactive oxygen species. Oxidative DNA damage is deleterious as it can directly modify the genetic information of DNA. The 7,8-dihydro-8-oxoguanine (8-oxoG) adduct is the most common mutagenic lesion that can lead to G:C to T:A transversions; these damages are normally processed by the Base Excision Repair pathway. Single-stranded binding (SSB) proteins from the oligonucleotide domain family are involved in DNA repair processes, such as the detection of DNA damage and recruitment of repair proteins. Using immunofluorescence we show that hSSB1 (a new human SSB) levels increase in response to oxidative damage (H202) and cells depleted of hSSB1 are hypersensitive to oxidative damage. We show that hSSB1 forms dimers and tetramers under oxidative conditions and that this oligomerisation is mediated by inter-domain disulfide bond formation. Furthermore, using Surface Plasmon Resonance, we show that oxidised hSSB1 binds 8-oxo-G damaged ssDNA with higher affinity than non-damaged ssDNA, highlighting a direct role for oxidised hSSB1 in the recognition of 8-oxo-G lesions. As oxidative stress is associated with aging, cancer and Alzheimer’s disease, understanding the molecular mechanism of how cells repair oxidative DNA damage will be crucial in the development of potential therapeutic treatments.