title: Genome-wide analysis to identify pathways affecting telomere-initiated senescence in budding yeast.
abstract: 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.
authors.affiliation: Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom.
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Chang
authors.forename: Conor
authors.initials: C
authors.lastname: Lawless
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Addinall
authors.forename: Sarah
authors.initials: S
authors.lastname: Oexle
authors.forename: Morgan
authors.initials: M
authors.lastname: Taschuk
authors.forename: Anil
authors.initials: A
authors.lastname: Wipat
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Wilkinson
authors.forename: David
authors.initials: D
authors.lastname: Lydall