title: The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation.
abstract: 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.
authors: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
authors: Hui-Yong
authors: HY
authors: Lian
authors: E Douglas
authors: ED
authors: Robertson
authors: Shin-ichiro
authors: S
authors: Hiraga
authors: Gina M
authors: GM
authors: Alvino
authors: David
authors: D
authors: Collingwood
authors: Heather J
authors: HJ
authors: McCune
authors: Akila
authors: A
authors: Sridhar
authors: Bonita J
authors: BJ
authors: Brewer
authors: M K
authors: MK
authors: Raghuraman
authors: Anne D
authors: AD
authors: Donaldson
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D001483:Base Sequence; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018741:Replication Origin; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; C520769:YKU70 protein, S cerevisiae; C081647:high affinity DNA-binding factor, S cerevisiae; C074461:RIF1 protein, S cerevisiae; D000123:Acetyltransferases; C489404:CDC7 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases