title: Inactivation of Cdc13p triggers MEC1-dependent apoptotic signals in yeast.
abstract: Inactivation of the budding yeast telomere binding protein Cdc13 results in abnormal telomeres (exposed long G-strands) and activation of the DNA damage checkpoint. In the current study, we show that inactivation of Cdc13p induces apoptotic signals in yeast, as evidenced by caspase activation, increased reactive oxygen species production, and flipping of phosphatidylserine in the cytoplasmic membrane. These apoptotic signals were suppressed in a mitochondrial (rho(o)) mutant. Moreover, mitochondrial proteins (e.g. MTCO3) were identified as multicopy suppressors of cdc13-1, suggesting the involvement of mitochondrial functions in telomere-initiated apoptotic signaling. These telomere-initiated apoptotic signals were also shown to depend on MEC1, but not TEL1, and were antagonized by MRE11. Our results are consistent with a model in which single-stranded G-tails in the cdc13-1 mutant trigger MEC1-dependent apoptotic signaling in yeast.
authors.affiliation: Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. qiha@umdnj.edu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Qi
authors.forename: Tsai-Kun
authors.initials: TK
authors.lastname: Li
authors.forename: Debbie
authors.initials: D
authors.lastname: Kuo
authors.forename: Alam
authors.initials: A
authors.lastname: Nur-E-Kamal
authors.forename: Leroy F
authors.initials: LF
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology; D034501:Telomere-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D015003:Yeasts / Q000166:cytology / Q000378:metabolism
chemical_list: C452219:Cdc13 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; D020169:Caspases