Abstract
Single-stranded DNA binding (SSB) proteins are essential to protect singe-stranded DNA (ssDNA) that exists as a result of several important DNA repair pathways in living cells. In humans, besides the well-characterised Replication Protein A (RPA) we have described another SSB termed human SSB1 (hSSB1, OBFC2B) and have shown that this protein is an important player in the maintenance of the genome. In this review we define the structural and biophysical details of how hSSB1 interacts with both DNA and other essential proteins. While the presence of the oligonucleotide/oligosaccharide (OB) domain ensures ssDNA binding by hSSB1, it has also been shown to self-oligomerise as well as interact with and being modified by several proteins highlighting the versatility that hSSB1 displays in the context of DNA repair. A detailed structural understanding of these processes will likely lead to the designs of tailored hSSB1 inhibitors as anti-cancer drugs in the near future.
Highlights
A Structural Perspective on the Regulation of Human Single-Stranded DNA Binding Protein 1 Function in DNA Repair
Besides the well-characterised Replication Protein A (RPA) we have described another Single-stranded DNA binding (SSB) termed human SSB1 and have shown that this protein is an important player in the maintenance of the genome
We have described a molecular model of the structural details governing the hSSB1 oligomerisation process [40], establishing that hSSB1 can exist as a functional tetramer, with monomermonomer and dimer-dimer interactions occurring at distinct surfaces of the OB domain, neither of which overlap with the singe-stranded DNA (ssDNA) binding surface (Fig. 3)
Summary
The most common feature among SSB proteins is the OB domain that binds DNA, RNA, and proteins [22,23,24] (Fig. 1, blue). This was further verified by mutational data from clonogenic survival assays and biolayer interferometry (BLI) studies. While base-stacking is a prominent structural feature of DNA binding of both EcoSSB and RPA, respectively, the number and nature of intercalating aromatic OB residues differ from hSSB1 [29,34,35]
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