title: Yeast DNA ligase IV mediates non-homologous DNA end joining.
abstract: The discovery of homologues from the yeast Saccharomyces cerevisiae of the human Ku DNA-end-binding proteins (HDF1 and KU80) has established that this organism is capable of non-homologous double-strand end joining (NHEJ), a form of DNA double-strand break repair (DSBR) active in mammalian V(D)J recombination. Identification of the DNA ligase that mediates NHEJ in yeast will help elucidate the function of the four mammalian DNA ligases in DSBR, V(D)J recombination and other reactions. Here we show that S. cerevisiae has two typical DNA ligases, the known DNA ligase I homologue CDC9 and the previously unknown DNA ligase IV homologue DNL4. dnl4 mutants are deficient in precise and end-processed NHEJ. DNL4 and HDF1 are epistatic in this regard, with the mutation of each having equivalent effects. dnl4 mutants are complemented by overexpression of Dnl4 but not of Cdc9, and deficiency of Dnl4 alone does not impair either cell growth or the Cdc9-mediated responses to ionizing and ultraviolet radiation. Thus, S. cerevisiae has two distinct and separate ligation pathways.
authors.affiliation: Washington University School of Medicine, Division of Laboratory Medicine, Department of Pathology, St Louis, Missouri 63110, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Wilson
authors.forename: U
authors.initials: U
authors.lastname: Grawunder
authors.forename: M R
authors.initials: MR
authors.lastname: Lieber
mesh_terms: D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism* / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014170:Transformation, Genetic
chemical_list: C000607890:CDC9 protein, S cerevisiae; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C000607891:DNL4 protein, S cerevisiae; D005656:Fungal Proteins; C000607892:LIG1 protein, human; C000607893:LIG4 protein, human; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C520769:YKU70 protein, S cerevisiae; C081647:high affinity DNA-binding factor, S cerevisiae; D004247:DNA; D002262:Carboxy-Lyases; C022378:phosphoribosylaminoimidazole carboxylase; D011088:DNA Ligases; D000072481:DNA Ligase ATP