title: More than 10% of yeast genes are related to genome stability and influence cellular senescence via rDNA maintenance.
abstract: Genome instability triggers cellular senescence and is a common cause of cancer. The ribosomal RNA genes (rDNA), due to their repetitive structure, form a fragile site with frequent rearrangements. To identify eukaryotic factors that connect reduced genome stability to senescence we screened 4,876 strains of a Saccharomyces cerevisiae deletion library for aberrant rDNA and found 708 genes that contribute to its upkeep. 28 mutants caused abnormalities in non-rDNA chromosomes and among them 12 mutants have abnormalities both in rDNA and in non-rDNA chromosomes. Many mutated genes have not previously been implicated with genome maintenance nor their homologues with tumorigenesis in mammals. The link between rDNA state and senescence was broken after deletion of factors related with DNA polymerase ϵ. These mutations also suppressed the short lifespan phenotype of a sir2 mutant, suggesting a model in which molecular events at the heart of the replication fork induce abnormal rDNA recombination and are responsible for the emergence of an aging signal.
authors.affiliation: National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540 Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Saka
authors.affiliation: National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540 Japan Sokendai, 1111 Yata, Mishima, Shizuoka 411-8540 Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540 Japan Laboratory of Genome Regeneration, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540 Japan Sokendai, 1111 Yata, Mishima, Shizuoka 411-8540 Japan Laboratory of Genome Regeneration, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan tako2015@iam.u-tokyo.ac.jp.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D056915:DNA Copy Number Variations; D004257:DNA Polymerase II / Q000502:physiology; D004260:DNA Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics*; D016681:Genome, Fungal; D042822:Genomic Instability; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology
chemical_list: D004271:DNA, Fungal; D004275:DNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; D004257:DNA Polymerase II