Publication:

Genome-Wide Analysis to Identify Pathways Affecting Telomere-Initiated Senescence in Budding Yeast (2011)

Author(s): Chang H, Lawless C, Addinall SG, Oexle S, Taschuk M, Wipat A, Wilkinson DJ, Lydall D

    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 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.

    • Type of Article: Full Research Article
    • Date: 01-08-2011
    • Journal: G3: Genes, Genomes, Genetics
    • Volume: 1
    • Issue: 3
    • Pages: 197-208
    • Publisher: Genetics Society of America
    • Publication type: Article
    • Bibliographic status: Published

    Keywords: telomere Saccharomyces cerevisiae senescence crisis

    Staff

    Professor David Lydall
    Professor of Genome Stability