Figure 3.

The “jackknife model” of nick sensing by ligase III. (a) DNA ligase III has an additional zinc finger (ZnF) that binds to nicks and gaps in DNA (b), stimulating DNA nick-joining by ligase III (c). The ZnF domain added in trans inhibits ligation by the catalytic core of ligase III, consistent with a competitive binding interaction. The ZnF and adjacent DNA-binding domain (DBD) constitute one DNA-binding surface of ligase III, and the catalytic core consisting of the nucleotidyltransferase (NTase) and OB-fold domains constitutes a second DNA-binding moiety. The jackknife model posits a handoff of the nicked DNA substrate from the ZnF-DBD to the catalytic core through protein motions resembling the opening and closing of blades of a jackknife. In this model, the ZnF-DBD initially recruits ligase III to an interruption in the DNA backbone, and then the DNA ends are engaged by the NTase-OB-fold catalytic core for the ligation reaction. (d) The ZnF also contributes strongly to the intermolecular ligation of linear DNA molecules. In this case, the two independent DNA-binding surfaces of ligase III (ZnF-DBD versus NTase-OB-fold) could align two DNAs for ligation (157). Abbreviations: AdD, adenylation domain; OB-fold, oligonucleotide/oligosaccharide binding fold.