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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, Nuclear*
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Base Sequence
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Chromosomes, Fungal
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Crosses, Genetic
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Cyclin B / chemistry
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Cyclin B / genetics
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Cyclin B / metabolism
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DNA Helicases*
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DNA Replication
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dimerization
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Heterozygote
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Ku Autoantigen
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Macromolecular Substances
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Mutagenesis, Site-Directed
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism*
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Oligodeoxyribonucleotides / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Recombination, Genetic*
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / physiology
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Saccharomyces cerevisiae Proteins*
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Telomere / genetics
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Telomere / metabolism*
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Telomere / ultrastructure
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Transcription Factors / metabolism
Substances
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Antigens, Nuclear
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Cyclin B
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DNA-Binding Proteins
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Fungal Proteins
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Macromolecular Substances
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Nuclear Proteins
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Oligodeoxyribonucleotides
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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YKU70 protein, S cerevisiae
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YKU80 protein, S cerevisiae
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high affinity DNA-binding factor, S cerevisiae
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DNA Helicases
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XRCC5 protein, human
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Xrcc6 protein, human
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Ku Autoantigen