Poster Presentation The 45th Lorne Conference on Protein Structure and Function 2020

Structural and biophysical details of hSSB1 oligomerisation in response to oxidative DNA damage (#308)

Serene El-Kamand 1 , Slobodan Jergic 2 , Teegan Lawson 1 , Nicholas E Dixon 2 , Liza Cubeddu 1 3 , Roland Gamsjaeger 1 3
  1. School of Science and Health, Western Sydney University , Penrith , NSW, Australia
  2. School of Chemistry, University of Wollongong, Wollongong, NSW, Australia
  3. School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia

The oxidative modification of DNA can result in a loss of genome integrity and mutagenesis. The most common form of oxidative DNA damage is the oxidation of the DNA base guanine to highly mutagenic 8-oxo-7,8-dihydro-guanine (8-oxoG). To protect the genome from mutagenesis, the modified base is removed through Base Excision Repair (BER), a process during which single stranded DNA (ssDNA) is exposed. Single stranded DNA binding proteins (SSBs) are a family of proteins that protect DNA, binding to sites of damage where DNA is unwound into its vulnerable single strands. Human Single Stranded DNA binding protein 1 (hSSB1), a novel human SSB, is crucial in the removal of mutagenic 8-oxoG through the BER pathway. The ability of hSSB1 to form dimers and tetramers (through the formation of disulfide bonds at the C81 and C99 residues) under oxidative conditions is critical in its function in BER. Here we use Nuclear Magnetic Resonance (NMR) spectroscopy and Surface Plasmon Resonance (SPR) experiments to examine the molecular details of hSSB1 oligomerisation in response to oxidative DNA damage.