title: Identification of DNA-PK in the arthropods. Evidence for the ancient ancestry of vertebrate non-homologous end-joining.
abstract: Cellular life depends upon the preservation and transmission of genetic material. Double stranded DNA breaks (DSBs) cause catastrophic gene loss in cell division and must be promptly and accurately repaired. In eukaryotes DSBs may be repaired by either non-homologous end-joining (NHEJ), single strand annealing or homologous recombination (HR). Vertebrate NHEJ has been shown to depend upon the DNA-dependent protein kinase (DNA-PK) consisting of the phosphatidylinositol 3 (PI 3)-kinase like (PIKK) catalytic sub-unit (DNA-PKcs) and the DNA targeting factor Ku. Our analysis of recently completed genomes found several novel PIKKs in Anopheles gambiae and Drosophila melanogaster including a novel mosquito DNA-PKcs orthologue, the first non-vertebrate DNA-PKcs described to date. We also detected a DNA-PKcs fragment in the high quality EST set of Apis mellifera ligustica (honey bee) suggesting that DNA-PK is a far older and more important eukaryotic complex than previously thought.
authors.affiliation: Department of Biochemistry, University of Cambridge, Old Addenbrookes site, 80 Tennis Court Road, CB2 1GA, Cambridge, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Doré
authors.forename: Adam C B
authors.initials: AC
authors.lastname: Drake
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Brewerton
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D034961:Antigens, Nuclear / Q000378:metabolism; D001181:Arthropods / Q000201:enzymology; D001516:Bees / Q000201:enzymology* / Q000235:genetics; D009033:Culicidae / Q000201:enzymology* / Q000235:genetics; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D000072200:Ku Autoantigen; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen