Document Detail


The Mec1p and Tel1p checkpoint kinases allow humanized yeast to tolerate chronic telomere dysfunctions by suppressing telomere fusions.
MedLine Citation:
PMID:  19007917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Enea Gino di Domenico; Cristina Auriche; Valeria Viscardi; Maria Pia Longhese; Eric Gilson; Fiorentina Ascenzioni
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-28
Journal Detail:
Title:  DNA repair     Volume:  8     ISSN:  1568-7864     ISO Abbreviation:  DNA Repair (Amst.)     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-12     Completed Date:  2009-04-07     Revised Date:  2009-06-02    
Medline Journal Info:
Nlm Unique ID:  101139138     Medline TA:  DNA Repair (Amst)     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  209-18     Citation Subset:  IM    
Affiliation:
Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Roma "La Sapienza", Roma, Italy.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Chromosomes, Fungal / metabolism
DNA Damage
DNA-Binding Proteins
Genomic Instability
Humans
Intracellular Signaling Peptides and Proteins / metabolism*
Microbial Viability
Protein-Serine-Threonine Kinases / metabolism*
Saccharomyces cerevisiae / cytology,  enzymology*
Saccharomyces cerevisiae Proteins / metabolism*
Telomere / enzymology*,  pathology*
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/LIF1 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; EC 2.7.11.1/MEC1 protein, S cerevisiae; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/TEL1 protein, S cerevisiae

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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