Single stranded DNA binding proteins (SSB) play a major role in cellular DNA processing events such as replication, recombination and repair and are central to maintaining the integrity of our genome. These processes require the DNA double helix to unwind, exposing less stable and highly vulnerable regions of single stranded DNA (ssDNA). SSB proteins bind ssDNA via a highly conserved oligonucleotide-binding (OB) domain and function to temporarily bind and protect exposed ssDNA generated during these events. The vital role of SSBs is evident from their ubiquitous presence in all forms of life.
We have discovered two novel SSBs in humans, hSSB1 and hSSB2 and revealed that both homologues are central to a range of DNA repair pathways. Both proteins are primarily involved in binding ssDNA and act very early in the damage response. This has provided us with the opportunity to study hSSB1 and hSSB2 as suitable targets to shut down highly active DNA repair processes in tumour cells. While we and others have been studying hSSB1 in great detail, comparatively little is known about hSSB2. In this work, we present NMR and biophysical data on the OB domain of hSSB2 that will contribute to uncovering the structural basis of ssDNA binding by this important SSB. This will ultimately aid in the development of SSB inhibitors for the use in novel anti-cancer therapeutics.