A new role of the rDNA and nucleolus in the nucleus—rDNA instability maintains genome integrity

Kobayashi, Takehiko

doi:10.1002/bies.20723

Cited by 160 publications

(154 citation statements)

References 34 publications

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“…rDNA copies are multiplied by repeated recombination, and their homogeneity is maintained by gene conversion events between the tandem repeats (Kobayashi, 2008). Recombination is induced by Fob1, which causes double-strand break formation.…”

Section: The Nucleolus Stress and Dna Damage Sensingmentioning

confidence: 99%

“…Recombination is induced by Fob1, which causes double-strand break formation. In yeast, at least, the histone deacetylase Sir2p also has a role in rDNA copy number regulation; in a sir2 mutant copy number fluctuated wildly, whereas in a fob1 mutant rDNA repeat fluctuation was reduced or eliminated (Kobayashi, 2008). In yeast, SIR1 and FOB1 affect cellular aging, sir1 mutants having a shorter lifespan and fob1 mutants a longer lifespan (Kobayashi, 2008).…”

Section: The Nucleolus Stress and Dna Damage Sensingmentioning

confidence: 99%

“…In yeast, at least, the histone deacetylase Sir2p also has a role in rDNA copy number regulation; in a sir2 mutant copy number fluctuated wildly, whereas in a fob1 mutant rDNA repeat fluctuation was reduced or eliminated (Kobayashi, 2008). In yeast, SIR1 and FOB1 affect cellular aging, sir1 mutants having a shorter lifespan and fob1 mutants a longer lifespan (Kobayashi, 2008). It was earlier shown that budding yeast cells accumulate extrachromosomal circles from the rDNA repeats preferentially in the mother cells as they age and that this accumulation in fact is a cause of aging (Sinclair and Guarente, 1997).…”

Section: The Nucleolus Stress and Dna Damage Sensingmentioning

confidence: 99%

“…There is a broad correlation between genome size and number of rDNA copies (Prokopowich et al, 2003), and this has led to a hypothesis that the rDNA may be acting as a sensor for DNA damage, protecting the rest of the genome by inducing DNA repair mechanisms or apoptosis. The extra copies present in the rDNA repeats would initially presumably buffer such damage, ensuring that sufficient undamaged copies were available for ribosome biosynthesis (Kobayashi, 2008). rDNA chromatin also seems to be able to affect the stability of heterochromatic repeats in trans, as loss of the NoRC component TIP5 leads to instability of microsatellite repeats (Guetg et al, 2010) and reduction in the number of Drosophila rDNA repeats themselves leads to a general release of heterochromatin silencing throughout the nucleus (Paredes and Maggert, 2009).…”

Section: The Nucleolus Stress and Dna Damage Sensingmentioning

confidence: 99%

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Nucleoli: Composition, Function, and Dynamics

2011

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Section: The Nucleolus Stress and Dna Damage Sensingmentioning

confidence: 99%

Section: The Nucleolus Stress and Dna Damage Sensingmentioning

confidence: 99%

Section: The Nucleolus Stress and Dna Damage Sensingmentioning

confidence: 99%

Section: The Nucleolus Stress and Dna Damage Sensingmentioning

confidence: 99%

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Nucleoli: Composition, Function, and Dynamics

2011

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“…Sequences within the repeated rDNA nucleate the nucleolus (8), a subnuclear structure which has functions in addition to its role in ribosome biosynthesis. The rDNA and nucleolus have played a prominent role in evolving theories of aging, metabolism, cell differentiation, cell cycle control, cancer progression, and gene regulation (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The rDNA is of particular interest in understanding heterochromatin because it is known to be regulated by epigenetic modification (20)(21)(22)(23)(24), is associated with both active and repressive protein modification (25,26), can affect variegation at unlinked genes (27,28), can itself induce variegation (29)(30)(31), and may change its size and regulation through the lifespan of an organism (32,33).…”

mentioning

confidence: 99%

Ribosomal DNA contributes to global chromatin regulation

Paredes

Maggert

2009

Proc. Natl. Acad. Sci. U.S.A.

143

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The 35S ribosomal RNA genes (rDNA) are organized as repeated arrays in many organisms. Epigenetic regulation of transcription of the rRNA results in only a subset of copies being transcribed, making rDNA an important model for understanding epigenetic chromatin modification. We have created an allelic series of deletions within the rDNA array of the Drosophila Y chromosome that affect nucleolus size and morphology, but do not limit steady-state rRNA concentrations. These rDNA deletions result in reduced heterochromatin-induced gene silencing elsewhere in the genome, and the extent of the rDNA deletion correlates with the loss of silencing. Consistent with this, chromosomes isolated from strains mutated in genes required for proper heterochromatin formation have very small rDNA arrays, reinforcing the connection between heterochromatin and the rDNA. In wild-type cells, which undergo spontaneous natural rDNA loss, we observed the same correlation between loss of rDNA and loss of heterochromatin-induced silencing, showing that the volatility of rDNA arrays may epigenetically influence gene expression through normal development and differentiation. We propose that the rDNA contributes to a balance between heterochromatin and euchromatin in the nucleus, and alterations in rDNA-induced or natural-affect this balance.Drosophila ͉ epigenetics ͉ heterochromatin ͉ nucleolus ͉ rDNA C hromatin within the nucleus is divided into cytologically heterochromatic and euchromatic compartments (1). This division reflects very different functional influences on gene expression (2). Many genes adopt more ''heterochromatin-like'' features when inactivated, including cytological appearance and association with specific proteins or post-translational modifications. This has led to hypotheses that similar mechanisms regulate facultatively inactivated genes or chromosomes, constitutively heterochromatic regions of the genome, and developmentally repressed genes (3). Understanding the interplay between heterochromatin and euchromatin, then, is fundamental in understanding the control of epigenetic regulation of the genome.Gene products involved in heterochromatin formation have been primarily identified by observing the effect of mutations on position effect variegation (PEV), which manifests as mosaic expression of a gene placed in a heterochromatic context. Many of these mutations act dominantly, thus the genes are thought to encode dosesensitive components of heterochromatin (4). Equally important to models of heterochromatin formation is the observation that the amount of constitutive heterochromatin in the nucleus affects heterochromatin-induced PEV at unlinked genes (5). In this model, gene products act as a ''source'' of heterochromatin forming potential, and DNA sequences destined to be heterochromatic as a ''sink.'' A balance is normally maintained between gene products and target DNA in the genome, although no proposed mechanism satisfactorily accounts for how this balance is maintained during division, determination, and differe...

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