Genome-Wide Analysis to Identify Pathways Affecting Telomere-Initiated Senescence in Budding Yeast

G3: Genes, Genomes, Genetics

Anil Wipat³  Stephen G. Addinall⁴  Hsin-Yu Chang¹  Sarah Oexle²  Darren J. Wilkinson³  Conor Lawless⁴  David Lydall⁴  Morgan Taschuk³ 

[1] Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United KingdomInstitute for Cell and Molecular Biosciences, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United KingdomInstitute for Cell and Molecular Biosciences, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom;Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United KingdomCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United KingdomCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United Kingdom;School of Computing Science and ^‡School of Mathematics and Statistics, Newcastle University, Newcastle upon Tyne, NE1 7RU, United KingdomCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United KingdomSchool of Computing Science and ^‡School of Mathematics and Statistics, Newcastle University, Newcastle upon Tyne, NE1 7RU, United KingdomSchool of Computing Science and ^‡School of Mathematics and Statistics, Newcastle University, Newcastle upon Tyne, NE1 7RU, United KingdomCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United KingdomCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United KingdomSchool of Computing Science and ^‡School of Mathematics and Statistics, Newcastle University, Newcastle upon Tyne, NE1 7RU, United KingdomCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United Kingdom;Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United KingdomCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United KingdomInstitute for Cell and Molecular Biosciences, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United KingdomInstitute for Cell and Molecular Biosciences, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United KingdomCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United KingdomCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United KingdomInstitute for Cell and Molecular Biosciences, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United KingdomCentre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, United Kingdom

关键词: telomere;    Saccharomyces cerevisiae;    senescence;    crisis;   

DOI  :  10.1534/g3.111.000216

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

In telomerase-deficient yeast cells, like equivalent mammalian cells, telomeres shorten over many generations until a period of senescence/crisis is reached. After this, a small fraction of cells can escape senescence, principally using recombination-dependent mechanisms. To investigate the pathways that affect entry into and recovery from telomere-driven senescence, we combined a gene deletion disrupting telomerase (est1Δ) with the systematic yeast deletion collection and measured senescence characteristics in high-throughput assays. As expected, the vast majority of gene deletions showed no strong effects on entry into/exit from senescence. However, around 200 gene deletions behaving similarly to a rad52Δest1Δ archetype (rad52Δ affects homologous recombination) accelerated entry into senescence, and such cells often could not recover growth. A smaller number of strains similar to a rif1Δest1Δ archetype (rif1Δ affects proteins that bind telomeres) accelerated entry into senescence but also accelerated recovery from senescence. Our genome-wide analysis identifies genes that affect entry into and/or exit from telomere-initiated senescence and will be of interest to those studying telomere biology, replicative senescence, cancer, and ageing. Our dataset is complementary to other high-throughput studies relevant to telomere biology, genetic stability, and DNA damage responses.

【 授权许可】

Unknown