title: The Mec1p and Tel1p checkpoint kinases allow humanized yeast to tolerate chronic telomere dysfunctions by suppressing telomere fusions.
abstract: In this work we report that budding yeasts carrying human-type telomeric repeats at their chromosome termini show a chronic activation of the Rad53-dependent DNA damage checkpoint pathway and a G2/M cell cycle delay. Furthermore, in the absence of either TEL1/ATM or MEC1/ATR genes, which encodes phosphatidylinositol 3-kinase-related kinases (PIKKs), we detected telomere fusions, whose appearance correlates with a reduced cell viability and a high rate of genome instability. Based on sequence analysis, telomere fusions occurred primarily between ultrashort telomeres. Microcolony formation assays argue against the possibility that fusion-containing cells are eliminated by PIKK-dependent signalling. These findings reveal that humanized telomeres in yeast cells are sensed as a chronically damaged DNA but do not greatly impair cell viability as long as the cells have a functional DNA damage checkpoint.
authors.affiliation: Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Roma "La Sapienza", Roma, Italy.
authors.forename: Enea Gino
authors.initials: EG
authors.lastname: di Domenico
authors.forename: Cristina
authors.initials: C
authors.lastname: Auriche
authors.forename: Valeria
authors.initials: V
authors.lastname: Viscardi
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Longhese
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Ascenzioni
mesh_terms: D001483:Base Sequence; D015825:Chromosomes, Fungal / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins; D042822:Genomic Instability; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D050296:Microbial Viability; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D016615:Telomere / Q000201:enzymology* / Q000473:pathology*
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C114091:LIF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae