title: Telomere-binding protein Taz1 controls global replication timing through its localization near late replication origins in fission yeast.
abstract: In eukaryotes, the replication of chromosome DNA is coordinated by a replication timing program that temporally regulates the firing of individual replication origins. However, the molecular mechanism underlying the program remains elusive. Here, we report that the telomere-binding protein Taz1 plays a crucial role in the control of replication timing in fission yeast. A DNA element located proximal to a late origin in the chromosome arm represses initiation from the origin in early S phase. Systematic deletion and substitution experiments demonstrated that two tandem telomeric repeats are essential for this repression. The telomeric repeats recruit Taz1, a counterpart of human TRF1 and TRF2, to the locus. Genome-wide analysis revealed that Taz1 regulates about half of chromosomal late origins, including those in subtelomeres. The Taz1-mediated mechanism prevents Dbf4-dependent kinase (DDK)-dependent Sld3 loading onto the origins. Our results demonstrate that the replication timing program in fission yeast uses the internal telomeric repeats and binding of Taz1.
authors.affiliation: Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan.
authors.forename: Atsutoshi
authors.initials: A
authors.lastname: Tazumi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Fukuura
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Nakato
authors.forename: Ami
authors.initials: A
authors.lastname: Kishimoto
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Takenaka
authors.forename: Shiho
authors.initials: S
authors.lastname: Ogawa
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Song
authors.forename: Tatsuro S
authors.initials: TS
authors.lastname: Takahashi
authors.forename: Takuro
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Hisao
authors.initials: H
authors.lastname: Masukata
mesh_terms: D001483:Base Sequence; D004261:DNA Replication / Q000502:physiology*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D018741:Replication Origin / Q000502:physiology; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C496523:Sld3 protein, S pombe; D034501:Telomere-Binding Proteins; C104344:taz1 protein, S pombe