title: Making ends meet in mycobacteria.
abstract: Genotoxic agents from endogenous and exogenous sources cause double-strand breaks (DSBs) in chromosomal DNA. Given the threat these lesions pose to viability, it is not surprising that multiple, conserved mechanisms exist for their detection, processing and repair. Previous studies have established both functional non-homologous end-joining (NHEJ) and homologous recombination (HR) systems in mycobacteria. However, relative pathway utilization in these organisms, which include the major human pathogen Mycobacterium tuberculosis, remains unclear. In this issue, Glickman and colleagues describe an elegant assay to distinguish DSB repair outcomes through simple phenotypic screening. By applying their novel reporter system to a panel of repair pathway mutants, they identify an unexpected role for single-strand annealing (SSA) in the related non-pathogen, Mycobacterium smegmatis. As such, these results expand the mycobacterial DSB repair pathway complement to three mechanisms that are distinguishable by their differential requirements for the DSB-resecting, helicase-nuclease machines, AdnAB and RecBCD. Notably, in an unexpected departure from classical models, they establish that mycobacterial RecBCD is a dedicated SSA nuclease, while AdnAB is required for RecA-dependent HR. Here, we consider the implications of their observations, which include the asymmetric cross-regulation of pathway function, for the role of DSB repair in mycobacterial pathogenesis.
authors.affiliation: MRC/NHLS/WITS Molecular Mycobacteriology Research Unit and DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Health Sciences, University of the Witwatersrand and the National Health Laboratory Service, PO Box 1038, Johannesburg 2000, South Africa. digby.warner@nhls.ac.za
authors.forename: Digby F
authors.initials: DF
authors.lastname: Warner
authors.forename: Valerie
authors.initials: V
authors.lastname: Mizrahi
mesh_terms: D002876:Chromosomes, Bacterial / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics* / Q000378:metabolism*; D043211:Exodeoxyribonuclease V / Q000378:metabolism; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000502:physiology*; D011938:Rec A Recombinases / Q000378:metabolism; D011995:Recombination, Genetic
chemical_list: D004269:DNA, Bacterial; D011938:Rec A Recombinases; D043211:Exodeoxyribonuclease V