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

  1. Lookup NU author(s)
  2. Dr Hsin Yu Chang
  3. Dr Conor Lawless
  4. Dr Stephen Addinall
  5. Morgan Taschuk
  6. Professor Anil Wipat
  7. Professor Darren Wilkinson
  8. Professor David Lydall
Author(s)Chang H, Lawless C, Addinall SG, Oexle S, Taschuk M, Wipat A, Wilkinson DJ, Lydall D
Publication type Article
JournalG3: Genes, Genomes, Genetics
ISSN (electronic)2160-1836
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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 rad52Δ est1Δ 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 rif1Δ est1Δ 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.
PublisherGenetics Society of America
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