DNA ligase

DNA ligase is an essential enzyme involved in joining breaks in the phosphodiester backbone of DNA by catalyzing the formation of covalent phosphodiester bonds between adjacent 5′ phosphate and 3′ hydroxyl ends in DNA. It is required for the completion of DNA replication (joining of Okazaki fragments on the lagging strand), for repairing single- and double-strand DNA breaks during DNA repair pathways (including base excision repair, nucleotide excision repair, and nonhomologous end joining), and for facilitating genetic recombination. DNA ligases are found in all forms of life and belong to the nucleotide transferase superfamily. Their mechanism involves an initial adenylation of a conserved lysine residue by ATP or NAD⁺, transfer of an AMP group to the 5′ phosphate DNA end forming a reactive intermediate, and finally phosphodiester bond formation linking DNA ends and releasing AMP. Multiple isoforms exist in higher organisms (e.g., DNA ligase I, III, IV in humans), each with distinct but sometimes overlapping functions—some specialized for specific repair processes (e.g., Ligase IV in nonhomologous end-joining). DNA ligases are critical for genome stability, and their dysfunction is linked to disease, while their unique functional domains in bacteria make them targets for antibacterial drug development. In research, DNA ligases are widely used in molecular cloning for the construction of recombinant DNA molecules.

Other names

Polynucleotide ligaseDNA-joining enzyme

Enzyme inhibition (small-molecule inhibitors block the ligase’s catalytic activity, preventing DNA strand joining and causing DNA break accumulation); Sensitization to DNA-damaging agents (inhibitors make cancer cells more susceptible to chemotherapy/radiation); Antibiotic action (selective targeting of bacterial NAD⁺-dependent DNA ligase disrupts bacterial DNA repair/replication, causing cell death)