Erring on the side of caution:
Non-homologous end joining and
bacterial genome plasticity/ evolution
Much of our current understanding of repair pathways in bacteria primarily comes from E. coli. However, it is becoming increasingly evident that other paradigms for repair should also be considered. For example, many other bacteria including pathogenic or opportunistic bacteria like Mycobacterium tuberculosis and Pseudomonas aeruginosa utilize an alternative translesion synthesis (TLS) pathway, called ImuABC, that is not found in E. coli. Why do bacteria have such diverse organization and dynamics of repair pathways? It is tempting to hypothesize that diversity in bacterial genome maintenance mechanisms may be driven by environmental or endogenous factors, such as inter-microbial interactions or genome GC content, that result in varying levels of specific stresses. For example, the idea that genome characteristics and presence/ absence of repair pathways can be interdependent is exemplified by our studies on bacterial end joining (NHEJ) repair. Although ubiquitously found in eukaryotes, NHEJ is not universally present in bacteria. To understand what could have led to the current distribution of NHEJ in bacteria, we carried out comparative genomics and phylogenetic analysis across ~6000 sequenced genomes. Our results showed that this repair trait was sporadically distributed across the phylogeny and suggested that this pattern of occurrence was consistent with the correlated evolution of NHEJ with key genome characteristics of genome size and growth rates. Given the central role these traits may play in determining the ability to carry out recombination, it is possible that the evolutionary history of bacterial NHEJ may have been shaped by the requirement for efficient DSB repair. Building on these observations we are now investigating a). how the presence of NHEJ can influence key bacterial genome characteristics and b). how cells regulate NHEJ action during repair.