Skip to main content
Log in

Ribosomal DNA instability and genome adaptability

  • Review
  • Published:
Chromosome Research Aims and scope Submit manuscript

Abstract

Ribosomes are large, multi-subunit ribonucleoprotein complexes, essential for protein synthesis. To meet the high cellular demand for ribosomes, all eukaryotes have numerous copies of ribosomal DNA (rDNA) genes that encode ribosomal RNA (rRNA), usually far in excess of the requirement for ribosome biogenesis. In all eukaryotes studied, rDNA genes are arranged in one or more clusters of tandem repeats localized to nucleoli. The tandem arrangement of repeats, combined with the high rates of transcription at the rDNA loci, and the difficulty of replicating repetitive sequences make the rDNA inherently unstable and particularly susceptible to large variations in repeat copy number. Despite mounting evidence suggesting extra-ribosomal functions of the rDNA, its repetitive nature has excluded it from traditional sequencing-based studies. However, more recently, several studies have revealed the unique potential of the rDNA to act as a “canary in the coalmine,” being particularly sensitive to genomic stresses and acting as a source of adaptive response. Here, we review evidence uncovering mechanisms of regulation of instability and copy number variation at the rDNA and their role in adaptation to the environment, which could serve to understand the basic principles governing the behavior of other tandem repeats and their role in shaping the genome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aguilera A, Garcia-Muse T (2012) R loops: from transcription byproducts to threats to genome stability. Mol Cell 46:115–124

    Article  CAS  PubMed  Google Scholar 

  • Akamatsu Y, Kobayashi T (2015) The human RNA polymerase I transcription terminator complex acts as a replication fork barrier that coordinates the progress of replication with rRNA transcription activity. Mol Cell Biol 35:1871–1881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Albert B, Leger-Silvestre I, Normand C, Ostermaier MK, Perez-Fernandez J et al (2011) RNA polymerase I-specific subunits promote polymerase clustering to enhance the rRNA gene transcription cycle. J Cell Biol 192:277–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bersani F, Lee E, Kharchenko PV, Xu AW, Liu M, Xega K, MacKenzie OC, Brannigan BW, Wittner BS, Jung H, Ramaswamy S, Park PJ, Maheswaran S, Ting DT, Haber DA (2015) Pericentromeric satellite repeat expansions through RNA-derived DNA intermediates in cancer. Proc Natl Acad Sci U S A 112:15148–15153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brahmachary M, Guilmatre A, Quilez J, Hasson D, Borel C, Warburton P, Sharp AJ (2014) Digital genotyping of macrosatellites and multicopy genes reveals novel biological functions associated with copy number variation of large tandem repeats. PLoS Genet 10:e1004418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brewer BJ, Lockshon D, Fangman WL (1992) The arrest of replication forks in the rDNA of yeast occurs independently of transcription. Cell 71:267–276

    Article  CAS  PubMed  Google Scholar 

  • Cahyani I, Cridge AG, Engelke DR, Ganley AR, O’Sullivan JM (2015) A sequence-specific interaction between the Saccharomyces cerevisiae rRNA gene repeats and a locus encoding an RNA polymerase I subunit affects ribosomal DNA stability. Mol Cell Biol 35:544–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carter NP (2007) Methods and strategies for analyzing copy number variation using DNA microarrays. Nat Genet 39:S16–S21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chestkov IV, Jestkova EM, Ershova ES, Golimbet VE, Lezheiko TV, Kolesina NY, Porokhovnik LN, Lyapunova NA, Izhevskaya VL, Kutsev SI, Veiko NN, Kostyuk SV (2018) Abundance of ribosomal RNA gene copies in the genomes of schizophrenia patients. Schizophr Res 197:305–314

    Article  CAS  PubMed  Google Scholar 

  • Dalgaard JZ, Godfrey EL, MacFarlane RJ (2011) Eukaryotic replication barriers: how, why and where forks stall. DNA Replication-Current Advances. pp 269–304

  • Diermeier SD, Nemeth A, Rehli M, Grummt I, Langst G (2013) Chromatin-specific regulation of mammalian rDNA transcription by clustered TTF-I binding sites. PLoS Genet 9:e1003786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diesch J, Hannan RD, Sanij E (2014) Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease. Cell Biosci 4:43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El Hage A, French SL, Beyer AL, Tollervey D (2010) Loss of topoisomerase I leads to R-loop-mediated transcriptional blocks during ribosomal RNA synthesis. Genes Dev 24:1546–1558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng J, Liang J, Li J, Li Y, Liang H, Zhao X, McNutt MA, Yin Y (2015) PTEN controls the DNA replication process through MCM2 in response to replicative stress. Cell Rep 13:1295–1303

    Article  CAS  PubMed  Google Scholar 

  • Flach J, Bakker ST, Mohrin M, Conroy PC, Pietras EM, Reynaud D, Alvarez S, Diolaiti ME, Ugarte F, Forsberg EC, le Beau MM, Stohr BA, Méndez J, Morrison CG, Passegué E (2014) Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells. Nature 512:198–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Forsburg SL, Shen KF (2017) Centromere stability: the replication connection. Genes (Basel) 8

  • Foss EJ, Lao U, Dalrymple E, Adrianse RL, Loe T, Bedalov A (2017) SIR2 suppresses replication gaps and genome instability by balancing replication between repetitive and unique sequences. Proc Natl Acad Sci U S A 114:552–557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • French SL, Osheim YN, Cioci F, Nomura M, Beyer AL (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gaillard H, Aguilera A (2016) Transcription as a threat to genome integrity. Annu Rev Biochem 85:291–317

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Muse T, Aguilera A (2016) Transcription-replication conflicts: how they occur and how they are resolved. Nat Rev Mol Cell Biol 17:553–563

    Article  CAS  PubMed  Google Scholar 

  • Gerber J-K, Gögel E, Berger C, Wallisch M, Müller F, Grummt I, Grummt F (1997) Termination of mammalian rDNA replication: polar arrest of replication fork movement by transcription termination factor TTF-I. Cell 90:559–567

    Article  CAS  PubMed  Google Scholar 

  • Gibbons JG, Branco AT, Yu S, Lemos B (2014) Ribosomal DNA copy number is coupled with gene expression variation and mitochondrial abundance in humans. Nat Commun 5:4850

    Article  CAS  PubMed  Google Scholar 

  • Gibbons JG, Branco AT, Godinho SA, Yu S, Lemos B (2015) Concerted copy number variation balances ribosomal DNA dosage in human and mouse genomes. Proc Natl Acad Sci U S A 112:2485–2490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ginno PA, Lott PL, Christensen HC, Korf I, Chedin F (2012) R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Mol Cell 45:814–825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez IL, Sylvester JE (1995) Complete sequence of the 43-kb human ribosomal DNA repeat: analysis of the intergenic spacer. Genomics 27:320–328

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez IL, Sylvester JE (2001) Human rDNA: evolutionary patterns within the genes and tandem arrays derived from multiple chromosomes. Genomics 73:255–263

    Article  CAS  PubMed  Google Scholar 

  • Hall LE, Mitchell SE, O'Neill RJ (2012) Pericentric and centromeric transcription: a perfect balance required. Chromosom Res 20:535–546

    Article  CAS  Google Scholar 

  • Hallgren J, Pietrzak M, Rempala G, Nelson PT, Hetman M (2014) Neurodegeneration-associated instability of ribosomal DNA. Biochim Biophys Acta 1842:860–868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamperl S, Cimprich KA (2016) Conflict resolution in the genome: how transcription and replication make it work. Cell 167:1455–1467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hannan RD, Drygin D, Pearson RB (2013) Targeting RNA polymerase I transcription and the nucleolus for cancer therapy. Expert Opin Ther Targets 17:873–878

    Article  CAS  PubMed  Google Scholar 

  • Henderson AS, Warburton D, Atwood KC (1972) Location of ribosomal DNA in the human chromosome complement. Proc Natl Acad Sci U S A 69:3394–3398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hernández P, Martín-Parras L, Martínez-Robles ML, Schvartzman JB (1993) Conserved features in the mode of replication of eukaryotic ribosomal RNA genes. EMBO J 12:1475–1485

    Article  PubMed  PubMed Central  Google Scholar 

  • Hindson BJ, Ness KD, Masquelier DA, Belgrader P, Heredia NJ, Makarewicz AJ, Bright IJ, Lucero MY, Hiddessen AL, Legler TC, Kitano TK, Hodel MR, Petersen JF, Wyatt PW, Steenblock ER, Shah PH, Bousse LJ, Troup CB, Mellen JC, Wittmann DK, Erndt NG, Cauley TH, Koehler RT, So AP, Dube S, Rose KA, Montesclaros L, Wang S, Stumbo DP, Hodges SP, Romine S, Milanovich FP, White HE, Regan JF, Karlin-Neumann GA, Hindson CM, Saxonov S, Colston BW (2011) High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem 83:8604–8610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hull RM, Cruz C, Jack CV, Houseley J (2017) Environmental change drives accelerated adaptation through stimulated copy number variation. PLoS Biol 15:e2001333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ide S, Watanabe K, Watanabe H, Shirahige K, Kobayashi T, Maki H (2007) Abnormality in initiation program of DNA replication is monitored by the highly repetitive rRNA gene array on chromosome XII in budding yeast. Mol Cell Biol 27:568–578

    Article  CAS  PubMed  Google Scholar 

  • Ide S, Miyazaki T, Maki H, Kobayashi T (2010) Abundance of ribosomal RNA gene copies maintains genome integrity. Science 327:693–696

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jack CV, Cruz C, Hull RM, Keller MA, Ralser M, Houseley J (2015) Regulation of ribosomal DNA amplification by the TOR pathway. Proc Natl Acad Sci U S A 112:9674–9679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R et al (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19:489–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim N, Jinks-Robertson S (2012) Transcription as a source of genome instability. Nat Rev Genet 13:204–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi T (2003) The replication fork barrier site forms a unique structure with Fob1p and inhibits the replication fork. Mol Cell Biol 23:9178–9188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi T (2014) Ribosomal RNA gene repeats, their stability and cellular senescence. Proc Jpn Acad Ser B Phys Biol Sci 90:119–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi T, Ganley AR (2005) Recombination regulation by transcription-induced cohesin dissociation in rDNA repeats. Science 309:1581–1584

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi T, Sasaki M (2017) rDNA stability is supported by many “buffer genes”—introduction to the Yeast rDNA Stability Database. FEMS Yeast Res 17

  • Kobayashi T, Heck DJ, 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Kunnev D, Rusiniak ME, Kudla A, Freeland A, Cady GK, Pruitt SC (2010) DNA damage response and tumorigenesis in Mcm2-deficient mice. Oncogene 29:3630–3638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kwan EX, Foss EJ, Tsuchiyama S, Alvino GM, Kruglyak L, Kaeberlein M, Raghuraman MK, Brewer BJ, Kennedy BK, Bedalov A (2013) A natural polymorphism in rDNA replication origins links origin activation with calorie restriction and lifespan. PLoS Genet 9:e1003329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laferte A, Favry E, Sentenac A, Riva M, Carles C et al (2006) The transcriptional activity of RNA polymerase I is a key determinant for the level of all ribosome components. Genes Dev 20:2030–2040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lang KS, Merrikh H (2018) The clash of macromolecular titans: replication-transcription conflicts in bacteria. Annu Rev Microbiol 72:71–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Little RD, Platt TH, Schildkraut CL (1993) Initiation and termination of DNA replication in human rRNA genes. Mol Cell Biol 13:6600–6613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Y, Chang Q, Zhang Y, Beezhold K, Rojanasakul Y et al (2009) Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3. Cell Cycle 8:2101–2109

    Article  CAS  PubMed  Google Scholar 

  • MacAlpine DM, Zhang Z, Kapler GM (1997) Type I elements mediate replication fork pausing at conserved upstream sites in the Tetrahymena thermophila ribosomal DNA minichromosome. Mol Cell Biol 17:4517–4525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malinovskaya EM, Ershova ES, Golimbet VE, Porokhovnik LN, Lyapunova NA, Kutsev SI, Veiko NN, Kostyuk SV (2018) Copy number of human ribosomal genes with aging: unchanged mean, but narrowed range and decreased variance in elderly group. Front Genet 9:306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mao J, Appel B, Schaack J, Sharp S, Yamada H, Söll D (1982) The 5S RNA genes of Schizosaccharomyces pombe. Nucleic Acids Res 10:487–500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masse E, Phoenix P, Drolet M (1997) DNA topoisomerases regulate R-loop formation during transcription of the rrnB operon in Escherichia coli. J Biol Chem 272:12816–12823

    Article  CAS  PubMed  Google Scholar 

  • Mayan M, Aragon L (2010) Cis-interactions between non-coding ribosomal spacers dependent on RNAP-II separate RNAP-I and RNAP-III transcription domains. Cell Cycle 9:4328–4337

    Article  CAS  PubMed  Google Scholar 

  • Mayer C, Schmitz KM, Li J, Grummt I, Santoro R (2006) Intergenic transcripts regulate the epigenetic state of rRNA genes. Mol Cell 22:351–361

    Article  CAS  PubMed  Google Scholar 

  • McNulty SM, Sullivan BA (2018) Alpha satellite DNA biology: finding function in the recesses of the genome. Chromosom Res 26:115–138

    Article  CAS  Google Scholar 

  • McStay B (2016) Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination. Genes Dev 30:1598–1610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Merrikh CN, Merrikh H (2018) Gene inversion increases evolvability in bacteria. bioRxiv 293571. https://doi.org/10.1101/293571

  • Michel AH, Kornmann B, Dubrana K, Shore D (2005) Spontaneous rDNA copy number variation modulates Sir2 levels and epigenetic gene silencing. Genes Dev 19:1199–1210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nadel J, Athanasiadou R, Lemetre C, Wijetunga NA, Broin PO et al (2015) RNA:DNA hybrids in the human genome have distinctive nucleotide characteristics, chromatin composition, and transcriptional relationships. Epigenetics Chromatin 8:46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Sullivan JM, Sontam DM, Grierson R, Jones B (2009) Repeated elements coordinate the spatial organization of the yeast genome. Yeast 26:125–138

    Article  CAS  PubMed  Google Scholar 

  • Oakes M, Nogi Y, Clark MW, Nomura M (1993) Structural alterations of the nucleolus in mutants of Saccharomyces cerevisiae defective in RNA polymerase I. Mol Cell Biol 13:2441–2455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oakes ML, Siddiqi I, Vu L, Aris J, Nomura M (1999) Transcription factor UAF, expansion and contraction of ribosomal DNA (rDNA) repeats, and RNA polymerase switch in transcription of yeast rDNA. Mol Cell Biol 19:8559–8569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paredes S, Branco AT, Hartl DL, Maggert KA, Lemos B (2011) Ribosomal DNA deletions modulate genome-wide gene expression: “rDNA-sensitive” genes and natural variation. PLoS Genet 7:e1001376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paul S, Million-Weaver S, Chattopadhyay S, Sokurenko E, Merrikh H (2013) Accelerated gene evolution through replication-transcription conflicts. Nature 495:512–515

    Article  CAS  PubMed  Google Scholar 

  • Peter J, De Chiara M, Friedrich A, Yue JX, Pflieger D et al (2018) Genome evolution across 1,011 Saccharomyces cerevisiae isolates. Nature 556:339–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petes TD (1979) Meiotic mapping of yeast ribosomal deoxyribonucleic acid on chromosome XII. J Bacteriol 138:185–192

    CAS  PubMed  PubMed Central  Google Scholar 

  • Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, Fiegler H, Shapero MH, Carson AR, Chen W, Cho EK, Dallaire S, Freeman JL, González JR, Gratacòs M, Huang J, Kalaitzopoulos D, Komura D, MacDonald JR, Marshall CR, Mei R, Montgomery L, Nishimura K, Okamura K, Shen F, Somerville MJ, Tchinda J, Valsesia A, Woodwark C, Yang F, Zhang J, Zerjal T, Zhang J, Armengol L, Conrad DF, Estivill X, Tyler-Smith C, Carter NP, Aburatani H, Lee C, Jones KW, Scherer SW, Hurles ME (2006) Global variation in copy number in the human genome. Nature 444:444–454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosato M, Kovarik A, Garilleti R, Rossello JA (2016) Conserved organisation of 45S rDNA sites and rDNA gene copy number among major clades of early land plants. PLoS One 11:e0162544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saiki R, Gelfand D, Stoffel S, Scharf S, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491

    Article  CAS  PubMed  Google Scholar 

  • Saka K, Takahashi A, Sasaki M, Kobayashi T (2016) More than 10% of yeast genes are related to genome stability and influence cellular senescence via rDNA maintenance. Nucleic Acids Res 44:4211–4221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salim D, Bradford WD, Freeland A, Cady G, Wang J, Pruitt SC, Gerton JL (2017) DNA replication stress restricts ribosomal DNA copy number. PLoS Genet 13:e1007006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez JA, Kim SM, Huberman JA (1998) Ribosomal DNA replication in the fission yeast, Schizosaccharomyces pombe. Exp Cell Res 238:220–230

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Gorostiaga A, Lopez-Estrano C, Krimer DB, Schvartzman JB, Hernandez P (2003) Transcription termination factor reb1p causes two replication fork barriers at its cognate sites in fission yeast ribosomal DNA in vivo. Mol Cell Biol 24:398–406

    Article  CAS  Google Scholar 

  • Sankar TS, Wastuwidyaningtyas BD, Dong Y, Lewis SA, Wang JD (2016) The nature of mutations induced by replication-transcription collisions. Nature 535:178–181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santoro R, Schmitz KM, Sandoval J, Grummt I (2010) Intergenic transcripts originating from a subclass of ribosomal DNA repeats silence ribosomal RNA genes in trans. EMBO Rep 11:52–58

    Article  CAS  PubMed  Google Scholar 

  • Shyian M, Mattarocci S, Albert B, Hafner L, Lezaja A, Costanzo M, Boone C, Shore D (2016) Budding yeast Rif1 controls genome integrity by inhibiting rDNA replication. PLoS Genet 12:e1006414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skourti-Stathaki K, Proudfoot NJ (2014) A double-edged sword: R loops as threats to genome integrity and powerful regulators of gene expression. Genes Dev 28:1384–1396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith JS, Caputo E, Boeke JD (1999) A genetic screen for ribosomal DNA silencing defects identifies multiple DNA replication and chromatin-modulating factors. Mol Cell Biol 19:3184–3197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stults DM, Killen MW, Pierce HH, Pierce AJ (2008) Genomic architecture and inheritance of human ribosomal RNA gene clusters. Genome Res 18:13–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stults DM, Killen MW, Williamson EP, Hourigan JS, Vargas HD, Arnold SM, Moscow JA, Pierce AJ (2009) Human rRNA gene clusters are recombinational hotspots in cancer. Cancer Res 69:9096–9104

    Article  CAS  PubMed  Google Scholar 

  • Ting DT, Lipson D, Paul S, Brannigan BW, Akhavanfard S, Coffman EJ, Contino G, Deshpande V, Iafrate AJ, Letovsky S, Rivera MN, Bardeesy N, Maheswaran S, Haber DA (2011) Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science 331:593–596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsekrekou M, Stratigi K, Chatzinikolaou G (2017) The nucleolus: in genome maintenance and repair. Int J Mol Sci 18

  • Udugama M, Sanij E, Voon HPJ, Son J, Hii L et al (2018) Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers. Proc Natl Acad Sci U S A 115:4737–4742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vogelstein B, Kinzler KW (1999) Digital PCR. Proc Natl Acad Sci 96:9236–9241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang M, Lemos B (2017) Ribosomal DNA copy number amplification and loss in human cancers is linked to tumor genetic context, nucleolus activity, and proliferation. PLoS Genet 13:e1006994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warburton PE, Hasson D, Guillem F, Lescale C, Jin X, Abrusan G (2008) Analysis of the largest tandemly repeated DNA families in the human genome. BMC Genomics 9:533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warner JR (1999) The economics of ribosome biosynthesis in yeast. Trends Biochem Sci 24:437–440

    Article  CAS  PubMed  Google Scholar 

  • Wiesendanger B, Lucchini R, Koller T, Sogo JM (1994) Replication fork barriers in the Xenopus rDNA. Nucleic Acids Res 22:5038–5046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wood V, Gwilliam R, Rajandream MA, Lyne M, Lyne R et al (2002) The genome sequence of Schizosaccharomyces pombe. Nature 415:871–880

    Article  CAS  PubMed  Google Scholar 

  • Wyandt H.E., Wilson G.N., Tonk V.S. (2017) Human chromosome variation: heteromorphism,polymorphism and pathogenesis. Springer, Singapore. https://doi.org/10.1007/978-981-10-3035-2

  • Xu B, Li H, Perry JM, Singh VP, Unruh J, Yu Z, Zakari M, McDowell W, Li L, Gerton JL (2017) Ribosomal DNA copy number loss and sequence variation in cancer. PLoS Genet 13:e1006771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu S, Lemos B (2018) The long-range interaction map of ribosomal DNA arrays. PLoS Genet 14:e1007258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zafiropoulos A, Tsentelierou E, Linardakis M, Kafatos A, Spandidos DA (2005) Preferential loss of 5S and 28S rDNA genes in human adipose tissue during ageing. Int J Biochem Cell Biol 37:409–415

    Article  CAS  PubMed  Google Scholar 

  • Zaratiegui M, Castel SE, Irvine DV, Kloc A, Ren J, Li F, de Castro E, Marín L, Chang AY, Goto D, Cande WZ, Antequera F, Arcangioli B, Martienssen RA (2011) RNAi promotes heterochromatic silencing through replication-coupled release of RNA Pol II. Nature 479:135–138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Mark Miller (Stowers Institute) for his help with illustrations. This work was done to fulfill, in part, the requirements for DS’s PhD thesis research as a student registered with the Open University.

Funding

This work was funded by the Stowers Institute for Medical Research.

Author information

Authors and Affiliations

Authors

Contributions

DS and JLG wrote, reviewed, and edited the manuscript.

Corresponding author

Correspondence to Jennifer L. Gerton.

Additional information

Responsible Editor: Beth A. Sullivan.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salim, D., Gerton, J.L. Ribosomal DNA instability and genome adaptability. Chromosome Res 27, 73–87 (2019). https://doi.org/10.1007/s10577-018-9599-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10577-018-9599-7

Keywords

Navigation