DNA ligases in the repair and replication of DNA

DNA ligases are critical enzymes of DNA metabolism. The reaction they catal yse (the joining of nicked DNA) is required in DNA replication and in DNA r epair pathways that require the re-synthesis of DNA. Most organisms express DNA ligases powered by ATP, but eubacteria appear to be unique in having ligases driven by NAD(+). Interestingly, despite prote in sequence and biochemical differences between the two classes of ligase, the structure of the adenylation domain is remarkably similar. Higher organ isms express a variety of different ligases, which appear to be targetted t o specific functions. DNA ligase I is required for Okazaki fragment joining and some repair pathways; DNA ligase II appears to be a degradation produc t of ligase III; DNA ligase III has several isoforms, which are involved In repair and recombination and DNA ligase IV is necessary for V(D)J recombin ation and non-homologous end-joining. Sequence and structural analysis of D NA ligases has shown that these enzymes are built around a common catalytic core, which is likely to be similar in three-dimensional structure to that of T7-bacteriophage ligase. The differences between the various ligases ar e likely to be mediated by regions outside of this common core, the structu res of which are not known. Therefore, the determination of these structure s, along with the structures of ligases bound to substrate DNAs and partner proteins ought to be seen as a priority. (C) 2000 Elsevier Science B.V. Al l rights reserved.