| Abstract: |
Repair of double-strand DNA breaks (DSBs) is critical to all living organisms. Scission of the phosphodiester backbone of both DNA strands is lethal if not repaired because such loss of linear chromosome integrity compromises chromosome replication and thereby prevents genome duplication. In contrast to some other types of DNA lesions which can be bypassed by damage-tolerant DNA polymerases, there is no known mechanism for the replication or transcription machinery to bypass a DSB, mandating their repair before replication or transcription can proceed. As such, multiple systems have evolved to repair DSBs, from bacterial to human cells (1 - 6). In the past decade, mycobacterial DNA repair systems in general, and mycobacterial DSB repair systems in particular, have received increasing attention. It has become clear that mycobacterial DSB repair differs substantially from the standard models of prokaryotic DSB repair derived from work in the Escherichia coli system. Most prominent among these differences is the existence of two additional DSB repair pathways that are not present in E. coli and were previously thought not to exist in bacteria: nonhomologous end joining (NHEJ) and single-strand annealing (SSA). Multiple other novel features of mycobacterial DSB repair have also been elucidated, making mycobacteria a new model system for the study of prokaryotic DSB repair. As now conceptualized, mycobacterial DSB repair actually most resembles DSB repair in budding yeast rather than other prokaryotes (Table 1). In addition to its emerging place as a model system, studies of mycobacterial DNA repair also are of great importance for understanding mechanisms of mutagenesis and genome diversification in Mycobacterium tuberculosis, the ultimate cause of antimicrobial resistance in M. tuberculosis (7). In addition to the information and references contained in this article, the reader is pointed to several excellent recently published reviews of mycobacterial DNA repair and mutagenesis (8 - 10). © 2014 American Society for Microbiology. |
