More Than 10% of Yeast Genes Are Related to Genome Stability and Influence Cellular Senescence Via RDNA Maintenance

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2016 Feb 26

PMID 26912831

Citations 26

Authors

Kimiko Saka

Akihiro Takahashi

Mariko Sasaki

Takehiko Kobayashi

Affiliations

Soon will be listed here.

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.

Citing Articles

RNA polymerase I mutant affects ribosomal RNA processing and ribosomal DNA stability.

Normand C, Dez C, Dauban L, Queille S, Danche S, Abderrahmane S RNA Biol. 2024; 21(1):1-16.

PMID: 39049162 PMC: 11275518. DOI: 10.1080/15476286.2024.2381910.

Shotgun metagenomics reveals interkingdom association between intestinal bacteria and fungi involving competition for nutrients.

Xie Z, Canalda-Baltrons A, dEnfert C, Manichanh C Microbiome. 2023; 11(1):275.

PMID: 38098063 PMC: 10720197. DOI: 10.1186/s40168-023-01693-w.

Contribution of Spontaneous Mutations to Quantitative and Molecular Variation at the Highly Repetitive rDNA Locus in Yeast.

Sharp N, Smith D, Driscoll G, Sun K, Vickerman C, Martin S Genome Biol Evol. 2023; 15(10).

PMID: 37847861 PMC: 10581546. DOI: 10.1093/gbe/evad179.

The long and short of rDNA and yeast replicative aging.

Smith J Proc Natl Acad Sci U S A. 2022; 119(23):e2205124119.

PMID: 35658078 PMC: 9191781. DOI: 10.1073/pnas.2205124119.

rDNA array length is a major determinant of replicative lifespan in budding yeast.

Hotz M, Thayer N, Hendrickson D, Schinski E, Xu J, Gottschling D Proc Natl Acad Sci U S A. 2022; 119(15):e2119593119.

PMID: 35394872 PMC: 9169770. DOI: 10.1073/pnas.2119593119.

References

Muller M, Lucchini R, Sogo J . Replication of yeast rDNA initiates downstream of transcriptionally active genes. Mol Cell. 2000; 5(5):767-77. DOI: 10.1016/s1097-2765(00)80317-2. View

Tang F, Watkins J, Bermudez M, Gray R, Gaban A, Portie K . A life-span extending form of autophagy employs the vacuole-vacuole fusion machinery. Autophagy. 2008; 4(7):874-86. DOI: 10.4161/auto.6556. View

Aguilera A . The connection between transcription and genomic instability. EMBO J. 2002; 21(3):195-201. PMC: 125829. DOI: 10.1093/emboj/21.3.195. View

Giaever G, Chu A, Ni L, Connelly C, Riles L, Veronneau S . Functional profiling of the Saccharomyces cerevisiae genome. Nature. 2002; 418(6896):387-91. DOI: 10.1038/nature00935. View

Takeuchi Y, Horiuchi T, Kobayashi T . Transcription-dependent recombination and the role of fork collision in yeast rDNA. Genes Dev. 2003; 17(12):1497-506. PMC: 196080. DOI: 10.1101/gad.1085403. View

Ivessa A, Lenzmeier B, Bessler J, Goudsouzian L, Schnakenberg S, Zakian V . The Saccharomyces cerevisiae helicase Rrm3p facilitates replication past nonhistone protein-DNA complexes. Mol Cell. 2003; 12(6):1525-36. DOI: 10.1016/s1097-2765(03)00456-8. View

Kobayashi T, Horiuchi T, Tongaonkar P, Vu L, Nomura M . SIR2 regulates recombination between different rDNA repeats, but not recombination within individual rRNA genes in yeast. Cell. 2004; 117(4):441-53. DOI: 10.1016/s0092-8674(04)00414-3. View

Burkhalter M, Sogo J . rDNA enhancer affects replication initiation and mitotic recombination: Fob1 mediates nucleolytic processing independently of replication. Mol Cell. 2004; 15(3):409-21. DOI: 10.1016/j.molcel.2004.06.024. View

Jazwinski S . Yeast replicative life span--the mitochondrial connection. FEMS Yeast Res. 2004; 5(2):119-25. DOI: 10.1016/j.femsyr.2004.04.005. View

10.

Van Dyck E, Foury F, Stillman B, Brill S . A single-stranded DNA binding protein required for mitochondrial DNA replication in S. cerevisiae is homologous to E. coli SSB. EMBO J. 1992; 11(9):3421-30. PMC: 556877. DOI: 10.1002/j.1460-2075.1992.tb05421.x. View

11.

Goyer C, Altmann M, Lee H, Blanc A, Deshmukh M, Woolford Jr J . TIF4631 and TIF4632: two yeast genes encoding the high-molecular-weight subunits of the cap-binding protein complex (eukaryotic initiation factor 4F) contain an RNA recognition motif-like sequence and carry out an essential function. Mol Cell Biol. 1993; 13(8):4860-74. PMC: 360119. DOI: 10.1128/mcb.13.8.4860-4874.1993. View

12.

Kennedy B, Austriaco Jr N, Guarente L . Daughter cells of Saccharomyces cerevisiae from old mothers display a reduced life span. J Cell Biol. 1994; 127(6 Pt 2):1985-93. PMC: 2120297. DOI: 10.1083/jcb.127.6.1985. View

13.

Wach A, Brachat A, Pohlmann R, Philippsen P . New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994; 10(13):1793-808. DOI: 10.1002/yea.320101310. View

14.

Sakai K, Ohta T, Minoshima S, Kudoh J, Wang Y, de Jong P . Human ribosomal RNA gene cluster: identification of the proximal end containing a novel tandem repeat sequence. Genomics. 1995; 26(3):521-6. DOI: 10.1016/0888-7543(95)80170-q. View

15.

Ellis N, Groden J, Ye T, Straughen J, Lennon D, Ciocci S . The Bloom's syndrome gene product is homologous to RecQ helicases. Cell. 1995; 83(4):655-66. DOI: 10.1016/0092-8674(95)90105-1. View

16.

Balciunas D, Ronne H . Three subunits of the RNA polymerase II mediator complex are involved in glucose repression. Nucleic Acids Res. 1995; 23(21):4421-5. PMC: 307399. DOI: 10.1093/nar/23.21.4421. View

17.

Kaufman P . Nucleosome assembly: the CAF and the HAT. Curr Opin Cell Biol. 1996; 8(3):369-73. DOI: 10.1016/s0955-0674(96)80012-3. View

18.

Samadashwily G, Raca G, Mirkin S . Trinucleotide repeats affect DNA replication in vivo. Nat Genet. 1997; 17(3):298-304. DOI: 10.1038/ng1197-298. View

19.

Freudenreich C, Kantrow S, Zakian V . Expansion and length-dependent fragility of CTG repeats in yeast. Science. 1998; 279(5352):853-6. DOI: 10.1126/science.279.5352.853. View

20.

Managbanag J, Witten T, Bonchev D, Fox L, Tsuchiya M, Kennedy B . Shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity. PLoS One. 2008; 3(11):e3802. PMC: 2583956. DOI: 10.1371/journal.pone.0003802. View