DNA double-strand breaks (DSBs) are one of the most lethal forms of DNA damage. Incorrectly repaired, or unrepaired breaks can lead to gross chromosomal rearrangements, aneuploidy and ultimately, carcinogenesis and cell-death. Non homologous end-joining (NHEJ) is a major DNA DSB repair pathway in both prokaryotes and eukaryotes. The prokaryotic NHEJ complex, comprising Ku and DNA ligase, assembles at DSBs to mediate repair of broken DNA ends. I will discuss how we have used a variety of cellular, biochemical and structural techniques to elucidate the mechanism of action of the prokaryotic NHEJ repair complex and how these studies contribute to our understanding of the molecular mechanisms that coordinate DNA break repair. We recently discovered Ku proteins in the genomes of phage and a direct role for NHEJ in viral life-cycle will also be discussed. References: Pitcher et al. (2007) J. Mol. Biol. 66, 391–; Bowater & Doherty (2006) PLOS Genetics 2, e8; Pitcher et al. (2006) Mol. Cell 23, 743-; Della et al. (2004) Science 306, 683-; Weller et al. (2002) Science 297, 1686-

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