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The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation.

DNA replication in Saccharomyces cerevisiae proceeds according to a temporal program. We have investigated the role of the telomere-binding Ku complex in specifying late replication of telomere-proximal sequences. Genome-wide analysis shows that regions extending up to 80 kb from telomeres replicate abnormally early in a yku70 mutant. We find that Ku does not appear to regulate replication time by binding replication origins directly, nor is its effect on telomere replication timing mediated by histone tail acetylation. We show that Ku instead regulates replication timing through its effect on telomere length, because deletion of the telomerase regulator Pif1 largely reverses the short telomere defect of a yku70 mutant and simultaneously rescues its replication timing defect. Consistent with this conclusion, deleting the genome integrity component Elg1 partially rescued both length and replication timing of yku70 telomeres. Telomere length-mediated control of replication timing requires the TG(1-3) repeat-counting component Rif1, because a rif1 mutant replicates telomeric regions early, despite having extended TG(1-3) tracts. Overall, our results suggest that the effect of Ku on telomere replication timing results from its impact on TG(1-3) repeat length and support a model in which Rif1 measures telomere repeat length to ensure that telomere replication timing is correctly programmed.

Pubmed ID: 21441303

Authors

  • Lian HY
  • Robertson ED
  • Hiraga S
  • Alvino GM
  • Collingwood D
  • McCune HJ
  • Sridhar A
  • Brewer BJ
  • Raghuraman MK
  • Donaldson AD

Journal

Molecular biology of the cell

Publication Data

May 15, 2011

Associated Grants

  • Agency: PHS HHS, Id: 18926
  • Agency: Cancer Research UK, Id: C1445/A10817
  • Agency: Cancer Research UK, Id: C1445/A2571
  • Agency: Medical Research Council, Id: G0600774

Mesh Terms

  • Acetylation
  • Acetyltransferases
  • Base Sequence
  • Cell Cycle
  • Cell Cycle Proteins
  • Chromosomes, Fungal
  • DNA Replication
  • DNA-Binding Proteins
  • Histones
  • Protein Processing, Post-Translational
  • Protein-Serine-Threonine Kinases
  • Replication Origin
  • Repressor Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sequence Deletion
  • Telomere
  • Telomere-Binding Proteins
  • Time Factors