The yeast Ku heterodimer is essential for protection of the telomere against nucleolytic and recombinational activities.

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.
Mesh Terms:
Antigens, Nuclear, Base Sequence, Chromosomes, Fungal, Crosses, Genetic, Cyclin B, DNA Helicases, DNA Replication, DNA-Binding Proteins, Dimerization, Fungal Proteins, Heterozygote, Macromolecular Substances, Mutagenesis, Site-Directed, Nuclear Proteins, Oligodeoxyribonucleotides, Recombinant Proteins, Recombination, Genetic, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Telomere, Transcription Factors
Curr. Biol.
Date: Jul. 02, 1998
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