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From Proteopedia

DNA Single Strand Binding Proteins

Function

During the initial stages of DNA replication, one of the enzymes associated with this process, DNA Helicase, breaks the hydrogen bonds between the complementary nucleotides of the two antiparallel strands. After this occurs, DNA, like any large macromolecule, is susceptible to forming secondary and more complex structures due to the varying properties of its constituent components. In this case, unwound DNA is highly susceptible to forming hairpin secondary structures due to the fact that many nucleotides on the same strand are complementary and will bind to each other. Luckily, over the course of billions of years of evolution, many prokaryotic and eukaryotic lineages developed a mechanism to prevent this hindrance to DNA replication--Single Strand DNA Binding Proteins. Typically, SSBs form tetramers that bind to each unwound individually and act as clamps that prevent the nucleotide chains from folding upon themselves. In essence, these protein complexes work to stabilize each DNA strand during the process of replication and streamline the process by preventing the formation of obstructive interactions. These proteins are coded for by DNA templates within the nuclei of both prokaryotic and eukaryotic cells. The genes associated with these proteins are transcribed and translated into SSBs, and are eventually transported back into the nucleus, where they operate as a part of the cellular machinery assisting in DNA replication(Pierce, 2013)

Interactions

During the DNA replication process SSB's interact with single strand DNA. Single-stranded DNA occurs during cellular respiration. It consists of the same base, sugar, and phosphate of double stranded DNA, but has lost the hydrogen bonds with the other strand. Single stranded DNA has a negative electronegativity due to the negative charge on the non-bridging oxygens in the phosphodiester bond (Shamoo, 2001).

The main interactions between the single-stranded binding protein and the single stranded DNA occur through electrostatic interactions, hydrogen bonding, and stacking interactions. The single strand DNA has a slightly negative charge due to a negative charge on one of the oxygens that make up the phosphodiester bond. Therefore, the SSB often has amino acids that have a positive charge, like lysine and arginine, on the surface of the . Amino acid side chains, amines, and carbonyl groups can also create hydrogen bonds with the backbone and bases of the DNA. All DNA nucleic acids have aromatic ring structures. These structures are rather flat. The SSBs use this common structure to make stacking interactions between the nucleic acid and the and planar regions on the SSB. These different methods allow the binding to be nonspecific to the order of nucleic acids (Shamoo, 2001).

An important structure in the binding of single-stranded proteins is the Oligonucleotide/oligosaccharide binding (OB) fold (Ashton, Bolderson, Cubeddu, O’Byrne, & Richard, 2013). This structure is made up of a five-stranded antiparallel beta barrel that ends in an . This structure provides a small area where the protein can interact with 2-5 nucleotides. The beta-barrel is tightly twisted which enhances the ability of the amino acid side chains to interact with the DNA (Shamoo, 2001). Some SSBs contain only on OB fold, whereas other more complex molecules have multiple folds for stronger interactions (Ashton et al., 2013).

Works Cited

Ashton, N. W., Bolderson, E., Cubeddu, L., O’Byrne, K. J., & Richard, D. J. (2013). Human single-stranded DNA binding proteins are essential for maintaining genomic stability. BMC Molecular Biology, 14, 9. https://doi.org/10.1186/1471-2199-14-9

Pierce, B. (2013). Genetics: A Conceptual Approach (5th ed.). W. H. Freeman.

Shamoo, Y. (2001). Single-stranded DNA-binding Proteins. In eLS. John Wiley & Sons, Ltd. https://doi.org/10.1038/npg.els.0002715