The Mec1p and Tel1p checkpoint kinases allow humanized yeast to tolerate chronic telomere dysfunctions by suppressing telomere fusions |
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| Authors: | Enea Gino di Domenico Cristina Auriche Valeria Viscardi Maria Pia Longhese Eric Gilson Fiorentina Ascenzioni |
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| Institution: | 1. Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Roma “La Sapienza”, Roma, Italy;2. Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy;3. Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS UMR5239, UCBL1, IFR128, 46 allée d’Italie, 69364 Lyon Cedex 07, France;1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8 Lavrentyev Ave, Novosibirsk 630090, Russian Federation;2. Department of Natural Sciences, Novosibirsk State University, 2 Pirogova St, Novosibirsk 630090, Russian Federation;3. Groupe «Réparation de l''ADN», Equipe Labellisée par la Ligue Nationale Contre le Cancer, CNRS UMR8200, Univ. Paris-Sud, Université Paris-Saclay, F-94805 Villejuif, France;4. Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France;1. Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovi?ova 6, 842 15 Bratislava, Slovakia;2. Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovi?ova 6, 842 15 Bratislava, Slovakia |
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| 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. |
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