title: The Saccharomyces cerevisiae Ku autoantigen homologue affects radiosensitivity only in the absence of homologous recombination.
abstract: In mammalian cells, all subunits of the DNA-dependent protein kinase (DNA-PK) have been implicated in the repair of DNA double-strand breaks and in V(D)J recombination. In the yeast Saccharomyces cerevisiae, we have examined the phenotype conferred by a deletion of HDF1, the putative homologue of the 70-kD subunit of the DNA-end binding Ku complex of DNA-PK. The yeast gene does not play a role in radiation-induced cell cycle checkpoint arrest in G1 and G2 or in hydroxyurea-induced checkpoint arrest in S. In cells competent for homologous recombination, we could not detect any sensitivity to ionizing radiation or to methyl methanesulfonate (MMS) conferred by a hdf1 deletion and indeed, the repair of DNA double-strand breaks was not impaired. However, if homologous recombination was disabled (rad52 mutant background), inactivation of HDF1 results in additional sensitization toward ionizing radiation and MMS. These results give further support to the notion that, in contrast to higher eukaryotic cells, homologous recombination is the favored pathway of double-strand break repair in yeast whereas other competing mechanisms such as the suggested pathway of DNA-PK-dependent direct break rejoining are only of minor importance.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: W
authors.initials: W
authors.lastname: Siede
authors.forename: A A
authors.initials: AA
authors.lastname: Friedl
authors.forename: I
authors.initials: I
authors.lastname: Dianova
authors.forename: F
authors.initials: F
authors.lastname: Eckardt-Schupp
authors.forename: E C
authors.initials: EC
authors.lastname: Friedberg
mesh_terms: D034961:Antigens, Nuclear; D002453:Cell Cycle / Q000235:genetics; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004171:Diploidy; D017353:Gene Deletion; D005800:Genes, Fungal; D006238:Haploidy; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011836:Radiation Tolerance / Q000235:genetics; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000276:immunology* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C520769:YKU70 protein, S cerevisiae; C081647:high affinity DNA-binding factor, S cerevisiae; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen