A Systems View of the Genome Guardians: Mapping the Signaling Circuitry Underlying Oligonucleotide/Oligosaccharide-Binding Fold Proteins

The oligonucleotide/oligosaccharide-binding (OB)-fold domain proteins are considered as genome guardians, whose functions are extending beyond genomic stability. The broad functional diversity of the OB-fold proteins is attributed to their protein-DNA, protein-RNA, and protein-protein interactions (PPI). To understand the connectivity of the human OB-fold proteins, we report here a systems-level approach. Specifically, we mapped all human OB-fold PPI networks and evaluated topological features such as network robustness and network hub, among others. We found that the OB-fold network comprised of 227 nodes forming 5523 interactions, and has a scale-free topology having UBA52, ATR, and TP53 as leading hub proteins that control efficient communication within the network. Furthermore, four different clusters and subclusters have been identified, which are implicated in diverse cellular processes, including DNA replication, repair, maintenance of genomic stability, RNA processing, spermatogenesis, complement system, and telomere maintenance. The importance of these clusters is further strengthened by knockout studies, which showed a significant decrease in topological properties. In summary, this study provides new insights on the role of OB-fold protein as genome guardians in regard to the underlying mechanism of signaling pathways, the roles of key regulators, and thus, offers new prospects as potential targets for diagnostics and therapeutics purposes.