CoChat
Sign Up
Cited by 167Telomeres, Telomerase, and SenescenceChromosomal and Genetic VariationsGenetics, Aging, and Longevity in Model Organisms

Ribosomal RNA gene repeats, their stability and cellular senescence

Open access
KOBAYASHI, Takehiko·2014·Proceedings of the Japan Academy, Series B
DOI 10.2183/pjab.90.119PMC PMC4055705
Open this paper in CoChat — free accountOpen PDF

Abstract

The ribosomal RNA gene (rDNA) repeats form a historically well-researched region in the chromosome. Their highly repetitive structure can be identified easily which has enabled studies on DNA replication, recombination, and transcription. The region is one of the most unstable regions in the genome because of deleterious recombination among the repeats. The ribosomal RNA gene repeats use a unique gene amplification system to restore the copy number after this has been reduced due to recombination. It has been shown that unstable features in the genome can accelerate cellular senescence that restricts the lifespan of a cell. Here, I will introduce a study by our group that shows how the stability of rDNA is maintained and affects lifespan. I propose that the ribosomal RNA gene repeats constitute a center from which the stability of the whole genome is regulated and the lifespan of the cell is controlled.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2183/pjab.90.119

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Maintaining a subset of rRNA genes in an inactive heterochromatic state is thought to be important for ensuring nucleolar structure and preventing recombination between rDNA repeats.

    “Second, maintaining a subset of rRNA genes in an inactive heterochromatic state is thought to be important for ensuring nucleolar structure and preventing recombination between rDNA repeats (22–24).”

    From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [24]

    The section “Transcription of rDNA and the role of non-transcribed repeat” (page not provided) says that about half the repeats are inactive and that these units bind condensin and provide space for DNA repair. The copy does not say that keeping those genes in a heterochromatic state ensures nucleolar structure or prevents recombination; it describes condensin's role in repair by homologous recombination. The “Regulation of the number of rDNA repeats” section separately describes Sir2-mediated repression of a promoter that increases recombination. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 39

  1. [1]Ellwood M. Nomura M. (1982) Chromosomal locations of the genes for rRNA in Escherichia coli K-12. J. Bacteriol. 149, 458– 468 6173374 PMC216529
  2. [2]Nomura M. Morgan E.A. Jaskunas S.R. (1977) Genetics of bacterial ribosomes. Annu. Rev. Genet. 11, 297– 347 339818
  3. [3]Warner J.R. (1999) The economics of ribosome biosynthesis in yeast. Trends Biochem. Sci. 24, 437– 440 10542411
  4. [4]Hartwell, L.H. (2008) Genetics: From Genes to Genomes, 3rd Edition. McGraw-Hill, U.S.A.
  5. [5]Brewer B.J. Fangman W.L. (1988) Mapping replication origins in yeast chromosomes. Bioessays 13, 317– 322 1759974
  6. [6]Ide, S. and Kobayashi, T. (2010) Analysis of DNA replication in Saccharomyces cerevisiae by two-dimensional and pulsed-field gel electrophoresis. Curr. Protoc. Cell Biol. Chapter 22, Unit 22.14. 21154549
  7. [7]Sakai M. Ohta T. Minoshima S. Kudoh J. Wang Y. de Jong P.J. Shimizu N. (1995) Human ribosomal RNA gene cluster: identification of the proximal end containing a novel tandem repeat sequence. Genomics 26, 521– 526 7607675
  8. [8]Gonzalez I.L. Sylvester J.E. (1995) Complete sequence of 43-kb human ribosomal DNA repeat: Analysis of the intergenic spacer. Genomics 27, 320– 328 7557999
  9. [9]Kobayashi T. Heck D.J. Nomura M. Horiuchi T. (1998) Expansion and contraction of ribosomal DNA repeats in Saccharomyces cerevisiae: requirement of replication fork blocking (Fob1) protein and the role of RNA polymerase I. Genes Dev. 12, 3821– 3830 9869636 PMC317266
  10. [10]Fangman W.L. Brewer B.J. (1991) Activation of replication origins within yeast chromosomes. Annu. Rev. Cell Biol. 7, 375– 402 1809350
  11. [11]Pasero P. Bensimon A. Schow E. (2002) Single-molecule analysis reveals clustering and epigenetic regulation of replication origins at the yeast rDNA locus. Genes Dev. 16, 2479– 2484 12368258 PMC187456
  12. [12]Araki H. (2011) Initiation of chromosomal DNA replication in eukaryotic cells; contribution of yeast genetics to the elucidation. Genes Genet. Syst. 86, 141– 149 21952204
  13. [13]Takeuchi Y. Horiuchi T. Kobayashi T. (2003) Transcription-dependent recombination and the role of fork collision in yeast rDNA. Genes Dev. 17, 1497– 1506 12783853 PMC196080
  14. [14]French S.L. Osheim Y.N. Cioci F. Nomura M. Beyer A.L. (2003) In exponentially growing Saccharomyces cerevisiae cells, rRNA synthesis is determined by the summed RNA polymerase I loading rate rather than by the number of active genes. Mol. Cell. Biol. 23, 1558– 1568 12588976 PMC151703
  15. [15]Ide S. Miyazaki T. Maki H. Kobayashi T. (2010) Abundance of ribosomal RNA gene copies maintains genome integrity. Science 327, 693– 696 20133573
  16. [16]Kobayashi T. Horiuchi T. Tongaonkar P. Vu L. Nomura M. (2004) SIR2 regulates recombination between different rDNA repeats, but not recombination within individual rRNA genes in yeast. Cell 117, 441– 453 15137938
  17. [17]Burkhalter M.D. Sogo J.M. (2004) rDNA enhancer affects replication initiation and mitotic recombination: Fob1 mediates nucleolytic processing independently of replication. Mol. Cell 15, 409– 421 15304221
  18. [18]Ide S. Saka K. Kobayashi T. (2013) Rtt109 prevents hyper-amplification of ribosomal RNA genes through histone modification in budding yeast. PLoS Genet. 9, e1003410 23593017 PMC3616922
  19. [19]Kobayashi T. Nomura M. Horiuch T. (2001) Identification of DNA cis-elements essential for expansion of ribosomal DNA repeats in Saccharomyces cerevisiae. Mol. Cell. Biol. 21, 136– 147 11113188 PMC88787
  20. [20]Kobayashi T. Ganley A.R. (2005) Recombination regulation by transcription-induced cohesin dissociation in rDNA repeats. Science 309, 1581– 1584 16141077
  21. [21]Kobayashi T. (2011) Regulation of ribosomal RNA gene copy number and its role in modulating genome integrity and evolutionary adaptability in yeast. Cell. Mol. Life Sci. 64, 1395– 1403 21207101 PMC3064901
  22. [22]Mayer C. Schmitz K. Grummt I. Santoro R. (2006) Intergenic transcripts regulate the epigenetic state of rRNA genes. Mol. Cell 22, 351– 361 16678107
  23. [23]Ganley A.R. Kobayashi T. (2007) Highly efficient concerted evolution in the ribosomal DNA repeats: total rDNA repeat variation revealed by whole-genome shotgun sequence data. Genome Res. 17, 184– 191 17200233 PMC1781350
  24. [24]Ganley A.R. Kobayashi T. (2011) Monitoring the rate and dynamics of concerted evolution in the ribosomal DNA repeats of Saccharomyces cerevisiae using experimental evolution. Mol. Biol. Evol. 28, 2883– 2891 21546356
  25. [26]Defossez P.A. Prusty R. Kaeberlein M. Lin S.J. Ferrigno P. Silver P.A. Keil R.L. Guarente L. (1999) Elimination of replication fork block protein Fob1 extends the life span of yeast mother cells. Mol. Cell 3, 447– 455 10230397
  26. [27]Jazwinsky S.M. (2001) New clues to old yeast. Mech. Ageing Dev. 122, 865– 882 11348655
  27. [28]Saka K. Ide S. Ganley A.R. Kobayashi T. (2013) Cellular senescence in yeast is regulated by rDNA noncoding transcription. Curr. Biol. 23, 1794– 1798 23993840
  28. [30]Lombard D.B. Pletcher S.D. Canto C. Auwerx J. (2011) Longevity hits a roadblock. Nature 477, 410– 411 21938058
  29. [31]Aguilaniu H. Gustafsson L. Rigoulet M. Nyström T. (2003) Asymmetric inheritance of oxidatively damaged proteins during cytokinesis. Science 299, 1751– 1753 12610228
  30. [32]Kobayashi T. (2008) A new role of the rDNA and nucleolus in the nucleus-rDNA instability maintains genome integrity. Bioessays 30, 267– 272 18293366
  31. [33]Ganley A.R.D. Ide S. Saka K. Kobayashi T. (2009) The effect of replication initiation on gene amplification in the rDNA and its relationship to aging. Mol. Cell 35, 683– 693 19748361
  32. [34]Dalgaard, J.Z., Godfrey, E.L. and MacFarlane, R.J. (2011) DNA Replication-Current Advances. Edited by Herve Seligmann, InTech, Chapter 13.
  33. [35]Stults D.M. Killen M.W. Williamson E.P. Hourigan J.S. Vargas H.D. Arnold S.M. Moscow J.A. Pierce A.J. (2009) Human rRNA gene clusters are recombinational hotspots in cancer. Cancer Res. 69, 9096– 9104 19920195
  34. [36]Caburet S. Conti C. Schurra C. Lebofsky R. Edelstein S.J. Bensimon A. (2005) Human ribosomal RNA gene arrays display a broad range of palindromic structures. Genome Res. 15, 1079– 1085 16024823 PMC1182220
  35. [37]Takai H. Smogorzewska A. de Lange T. (2003) DNA damage foci at dysfunctional telomeres. Curr. Biol. 13, 1549– 1556 12956959
  36. [40]Kobayashi T. (2011) How does genome instability affect lifespan?: roles of rDNA and telomeres. Genes Cells 16, 617– 624 21605287 PMC3178783
  37. [41]Greider C.W. Blackburn E.H. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405– 413 3907856
  38. [42]Long E.O. Dawid I.B. (1980) Repeated genes in eukaryotes. Annu. Rev. Biochem. 49, 727– 764 6996571
  39. [43]Kobayashi T. (2009) Collaboration of replication, recombination and noncoding transcription for gene amplification. Protein, Nucleic Acid Enzyme 54, 537– 542 21089505

Cited by

Sorted by citations

Authors
KOBAYASHI, T.
Affiliations
National Institute of Genetics (JP)
Corresponding author
KOBAYASHI, Takehiko
ORCID
KOBAYASHI, Takehiko
Venue
Proceedings of the Japan Academy, Series B
Publisher
Japan Academy
Published
2014
Volume
90
Issue
4
Pages
119-129
ISSN
  • 0386-2208 (ISSN-L)
  • 1349-2896
DOI
10.2183/pjab.90.119
PMC
PMC4055705
OpenAlex
W2082238938
Cited by
167
References
4
Citations by year
2026: 4 · 2025: 9 · 2024: 15 · 2023: 19 · 2022: 13 · 2021: 25 · 2020: 14 · 2019: 26 · 2018: 11 · 2017: 5 · 2016: 18 · 2015: 7
FWCI
1.17
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the Japan Academy Series B (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology (23114002)
  • Japan Society for the Promotion of Science
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
ribosomal DNA, genome stability, cellular senescence, gene amplification, copy number, lifespan, DNA replication, transcription
MeSH terms
Animals, DNA, Ribosomal, Humans, Repetitive Sequences, Nucleic Acid, RNA, Ribosomal, Cellular Senescence, Genes, rRNA, RNA Stability

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review