title: The yeast Ku heterodimer is essential for protection of the telomere against nucleolytic and recombinational activities.
abstract: The Ku heterodimer, conserved in a wide range of eukaryotes, plays a multiplicity of roles in yeast. First, binding of Ku, which is composed of a 70 kDa (Hdf1p) and an 80 kDa (Hdf2p) subunit [1-3], to double-strand breaks promotes non-homologous end-to-end joining of DNA [3]. Second, Ku appears to participate in DNA replication, regulating both the number of rounds of replication permissible within the cell cycle and the structure of the initiation complex [3,4]. Furthermore, mutations in HDF1 or HDF2 rapidly reduce telomeric poly (TG1-3) tract size [1-3], hinting also at a possible telomeric function of Ku. We show here that the two subunits of the Ku heterodimer play a key role in maintaining the integrity of telomere structure. Mutations in either Ku subunit increased the single-strandedness of the telomere in a cell-cycle-independent fashion, unlike wild-type cells which form 3' poly(TG1-3) overhangs exclusively in late S phase [5]. In addition, mutations enhanced the instability of elongated telomeres to degradation and recombination. Both Ku subunits genetically interacted with the putative single-stranded telomere-binding protein Cdc13p. We propose that Ku protects the telomere against nucleases and recombinases.
authors.affiliation: Department of Biochemistry, Tulane University Medical Center, New Orleans, Louisiana 70112, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Polotnianka
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: A J
authors.initials: AJ
authors.lastname: Lustig
mesh_terms: D034961:Antigens, Nuclear; D001483:Base Sequence; D015825:Chromosomes, Fungal; D003433:Crosses, Genetic; D019926:Cyclin B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D000072200:Ku Autoantigen; D046911:Macromolecular Substances; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D016615:Telomere / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D019926:Cyclin B; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C520769:YKU70 protein, S cerevisiae; C520770:YKU80 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