In silico identification of a multi-functional regulatory protein involved in Holliday junction resolution in bacteria

Background: Homologous recombination is a fundamental cellular process that is most widely used by cells to rearrange genes and accurately repair DNA double-strand breaks. It may result in the formation of a critical intermediate named Holliday junction, which is a four-way DNA junction and needs to be resolved to allow chromosome segregation. Different Holliday junction resolution systems and enzymes have been characterized from all three domains of life. In bacteria, the RuvABC complex is the most important resolution system. Results: In this study, we conducted comparative genomics studies to identify a novel DNA-binding protein, YebC, which may serve as a key transcriptional regulator that mainly regulates the gene expression of RuvABC resolvasome in bacteria. On the other hand, the presence of YebC orthologs in some organisms lacking RuvC implied that it might participate in other biological processes. Further phylogenetic analysis of YebC protein sequences revealed two functionally different subtypes: YebC_I and YebC_II. Distribution of YebC_I is much wider than YebC_II. Only YebC_I proteins may play an important role in regulating RuvABC gene expression in bacteria. Investigation of YebC-like proteins in eukaryotes suggested that they may have originated from YebC_II proteins and evolved a new function as a specific translational activator in mitochondria. Finally, additional phylum-specific genes associated with Holliday junction resolution were predicted. Conclusions: Overall, our data provide new insights into the basic mechanism of Holliday junction resolution and homologous recombination in bacteria.