The Mec1p and Tel1p checkpoint kinases allow humanized yeast to tolerate chronic telomere dysfunctions by suppressing telomere fusions
| Autor: | Maria Pia Longhese, Enea Gino Di Domenico, Cristina Auriche, Fiorentina Ascenzioni, Valeria Viscardi, Eric Gilson |
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| Přispěvatelé: | di Domenico, E, Auriche, C, Viscardi, V, Longhese, M, Gilson, E, Ascenzioni, F |
| Rok vydání: | 2008 |
| Předmět: |
Checkpoints
Genome instability Saccharomyces cerevisiae Proteins Yeast Telomere Telomere fusion Checkpoints TEL1 MEC1 BIO/18 - GENETICA Saccharomyces cerevisiae Biology Protein Serine-Threonine Kinases Biochemistry Genomic Instability chemistry.chemical_compound Humans MEC1 Molecular Biology Gene Telomere fusion Telomere-binding protein Microbial Viability Base Sequence Checkpoint Kinase TEL1 Intracellular Signaling Peptides and Proteins Cell Biology G2-M DNA damage checkpoint Cell cycle Telomere Molecular biology Yeast DNA-Binding Proteins chemistry Chromosomes Fungal DNA DNA Damage |
| Zdroj: | DNA repair. 8(2) |
| ISSN: | 1568-7864 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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