title: Identification of Saccharomyces cerevisiae DNA ligase IV: involvement in DNA double-strand break repair.
abstract: DNA ligases catalyse the joining of single and double-strand DNA breaks, which is an essential final step in DNA replication, recombination and repair. Mammalian cells have four DNA ligases, termed ligases I-IV. In contrast, other than a DNA ligase I homologue (encoded by CDC9), no other DNA ligases have hitherto been identified in Saccharomyces cerevisiae. Here, we report the identification and characterization of a novel gene, LIG4, which encodes a protein with strong homology to mammalian DNA ligase IV. Unlike CDC9, LIG4 is not essential for DNA replication, RAD52-dependent homologous recombination nor the repair of UV light-induced DNA damage. Instead, it encodes a crucial component of the non-homologous end-joining (NHEJ) apparatus, which repairs DNA double-strand breaks that are generated by ionizing radiation or restriction enzyme digestion: a function which cannot be complemented by CDC9. Lig4p acts in the same DNA repair pathway as the DNA end-binding protein Ku. However, unlike Ku, it does not function in telomere length homeostasis. These findings indicate diversification of function between different eukaryotic DNA ligases. Furthermore, they provide insights into mechanisms of DNA repair and suggest that the NHEJ pathway is highly conserved throughout the eukaryotic kingdom.
authors.affiliation: Wellcome/CRC Institute and Department of Zoology, University of Cambridge, UK. sht@mole.bio.cam.ac.uk
authors.forename: S H
authors.initials: SH
authors.lastname: Teo
authors.forename: S P
authors.initials: SP
authors.lastname: Jackson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism; D018390:Gene Targeting; D005800:Genes, Fungal; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D016615:Telomere / Q000235:genetics / Q000378:metabolism
chemical_list: C000607890:CDC9 protein, S cerevisiae; D017931:DNA Primers; D004271:DNA, Fungal; C000607891:DNL4 protein, S cerevisiae; C000607892:LIG1 protein, human; C000607893:LIG4 protein, human; D011088:DNA Ligases; D000072481:DNA Ligase ATP