title: Cdk1 regulates the temporal recruitment of telomerase and Cdc13-Stn1-Ten1 complex for telomere replication.
abstract: In budding yeast (Saccharomyces cerevisiae), the cell cycle-dependent telomere elongation by telomerase is controlled by the cyclin-dependent kinase 1 (Cdk1). The telomere length homeostasis is balanced between telomerase-unextendable and telomerase-extendable states that both require Cdc13. The recruitment of telomerase complex by Cdc13 promotes telomere elongation, while the formation of Cdc13-Stn1-Ten1 (CST) complex at the telomere blocks telomere elongation by telomerase. However, the cellular signaling that regulates the timing of the telomerase-extendable and telomerase-unextendable states is largely unknown. Phosphorylation of Cdc13 by Cdk1 promotes the interaction between Cdc13 and Est1 and hence telomere elongation. Here, we show that Cdk1 also phosphorylates Stn1 at threonine 223 and serine 250 both in vitro and in vivo, and these phosphorylation events are essential for the stability of the CST complexes at the telomeres. By controlling the timing of Cdc13 and Stn1 phosphorylations during cell cycle progression, Cdk1 regulates the temporal recruitment of telomerase complexes and CST complexes to the telomeres to facilitate telomere maintenance.
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Chang-Ching
authors.initials: CC
authors.lastname: Liu
authors.forename: Veena
authors.initials: V
authors.lastname: Gopalakrishnan
authors.forename: Lai-Fong
authors.initials: LF
authors.lastname: Poon
authors.forename: TingDong
authors.initials: T
authors.lastname: Yan
authors.forename: Shang
authors.initials: S
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004261:DNA Replication; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D059505:Telomere Homeostasis; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D020798:Two-Hybrid System Techniques
chemical_list: C452219:Cdc13 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C428109:Stn1 protein, S cerevisiae; C512860:TEN1 protein, S cerevisiae; D034501:Telomere-Binding Proteins; D013912:Threonine; D012694:Serine; D016203:CDC2 Protein Kinase; D019098:Telomerase