title: ATP-dependent DNA ligases.
abstract: By catalyzing the joining of breaks in the phosphodiester backbone of duplex DNA, DNA ligases play a vital role in the diverse processes of DNA replication, recombination and repair. Three related classes of ATP-dependent DNA ligase are readily apparent in eukaryotic cells. Enzymes of each class comprise catalytic and non-catalytic domains together with additional domains of varying function. DNA ligase I is required for the ligation of Okazaki fragments during lagging-strand DNA synthesis, as well as for several DNA-repair pathways; these functions are mediated, at least in part, by interactions between DNA ligase I and the sliding-clamp protein PCNA. DNA ligase III, which is unique to vertebrates, functions both in the nucleus and in mitochondria. Two distinct isoforms of this enzyme, differing in their carboxy-terminal sequences, are produced by alternative splicing: DNA ligase IIIalpha has a carboxy-terminal BRCT domain that interacts with the mammalian DNA-repair factor XrccI, but both alpha and beta isoforms have an amino-terminal zinc-finger motif that appears to play a role in the recognition of DNA secondary structures that resemble intermediates in DNA metabolism. DNA ligase IV is required for DNA non-homologous end joining pathways, including recombination of the V(D)J immunoglobulin gene segments in cells of the mammalian immune system. DNA ligase IV forms a tight complex with Xrcc4 through an interaction motif located between a pair of carboxy-terminal BRCT domains in the ligase. Recent structural studies have shed light on the catalytic function of DNA ligases, as well as illuminating protein-protein interactions involving DNA ligases IIIalpha and IV.
authors: Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, King's Buildings, Edinburgh EH9 3JR, UK. s.a.macneill@ed.ac.uk
authors: Ina V
authors: IV
authors: Martin
authors: Stuart A
authors: SA
authors: MacNeill
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D011088:DNA Ligases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019143:Evolution, Molecular; D008928:Mitochondria / Q000201:enzymology; D008958:Models, Molecular; D017434:Protein Structure, Tertiary
chemical_list: D000255:Adenosine Triphosphate; D011088:DNA Ligases