In eukaryotic cells, repair of DNA double-strand breaks (DSBs) by the nonhomologous end-joining (NHEJ) pathway is critical for genomic stability. A functionally homologous repair apparatus, composed of Ku and a multifunctional DNA ligase (LigD), has recently been identified in many prokaryotes. Eukaryotic organisms employ a large number of factors to repair breaks by NHEJ. In contrast, the bacterial NHEJ complex is a two-component system that, despite its relative simplicity, possesses all of the break-recognition, end-processing, and ligation activities required to facilitate the complex task of DSB repair. Here, we review recent discoveries on the structure and function of the bacterial NHEJ repair apparatus. In particular, we discuss the evolutionary origins of this DSB repair pathway, how the diverse activities within the prokaryotic end-joining complex cooperate to facilitate DSB repair, the physiological roles of bacterial NHEJ, and finally, the essential function of NHEJ in the life cycle of mycobacteriophage.

Nonhomologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway required to maintain genome stability. Many prokaryotes possess a minimalist NHEJ apparatus required to repair DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). The crystal structure of Mycobacterium tuberculosis polymerase domain of LigD mediating the synapsis of two noncomplementary DNA ends revealed a variety of interactions, including microhomology base pairing, mismatched and flipped-out bases, and 3' termini forming hairpin-like ends. Biochemical and biophysical studies confirmed that polymerase-induced end synapsis also occurs in solution. We propose that this DNA synaptic structure reflects an intermediate bridging stage of the NHEJ process, before end processing and ligation, with both the polymerase and the DNA sequence playing pivotal roles in determining the sequential order of synapsis and remodeling before end joining.