Successful genome duplication relies on a close interplay between the DNA replication and genetic recombination machinery. This is because replisomes frequently encounter roadblocks such as lesions or bound proteins, resulting in situations where replication forks become inactivated. In this inactivated state, forks cannot progress past the impediment and the replisome may be partly or completely disassembled. Failure to rescue stalled forks and restart replication leads to genome instability, underlying the importance of this process in both prokaryotes and eukaryotes.We elucidated the mechanism of fork regression in E. coli and resolved a major conflict that had persisted in the field for many years. We showed that this reaction is driven by a specialized DNA helicase known as RecG, using a combination of bulk-phase biochemistry and single-molecule biophysics, In the process of determining this complex mechanism, we demonstrated how the essential single-strand binding protein (SSB) interacts with RecG. In the course of these studies,we have revealed the mechanism of action of the SSB interactome using super-resolution, structured illumination microscopy, single-molecule biophysics, and bacteriology. We show that interactome regulation is mediated by the linker/oligosaccharide-oligonucleotide binding fold (OB-fold) network of interactions. This network of interactions forms when one or more PXXP motifs in the linker of SSB bind to an OB-fold in a partner. As OB-folds are critical to the essence of the linker/OB-fold network of interactions, and they are found in multiple interactome partners, the SSB interactome is classified as the first family of prokaryotic OB-fold genome guardians.