title: Chromosome end protection plasticity revealed by Stn1p and Ten1p bypass of Cdc13p.
abstract: Genome stability necessitates a mechanism to protect the termini of linear chromosomes from inappropriate degradation or recombination. In many species this protection depends on 'capping' proteins that bind telomeric DNA. The budding yeast Cdc13p binds single-stranded telomeric sequences, prevents lethal degradation of chromosome ends and regulates telomere extension by telomerase. Two Cdc13-interacting proteins, Stn1p and Ten1p, are also required for viability and telomere length regulation. It has been proposed that Cdc13p DNA binding directs a Cdc13p-Stn1p-Ten1p complex to telomeres to mediate end protection. However, the functional significance of these protein interactions, and their respective roles in maintaining telomere integrity, remain undefined. Here, we show that co-overexpressing TEN1 with a truncated form of STN1 efficiently bypasses the essential role of CDC13. We further show that this truncated Stn1p binds directly to Pol12p, a polymerase alpha-primase regulatory subunit, and that Pol12 activity is required for CDC13 bypass. Thus, Stn1p and Ten1p control a Cdc13p-independent telomere capping mechanism that is coupled to the conventional DNA replication machinery.
authors.affiliation: Graduate Program in Cell, Molecular and Developmental Biology, 5429 Boyce Hall, University of California Riverside, Riverside, CA 92521, USA.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Petreaca
authors.forename: Huan-Chih
authors.initials: HC
authors.lastname: Chiu
authors.forename: Holly A
authors.initials: HA
authors.lastname: Eckelhoefer
authors.forename: Charles
authors.initials: C
authors.lastname: Chuang
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Constance I
authors.initials: CI
authors.lastname: Nugent
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D042822:Genomic Instability / Q000235:genetics; D046911:Macromolecular Substances / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C452219:Cdc13 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D029701:Saccharomyces cerevisiae Proteins; C428109:Stn1 protein, S cerevisiae; C512860:TEN1 protein, S cerevisiae; D034501:Telomere-Binding Proteins