Nomura, M., Morgan, E. A. & Jaskunas, S. R. Genetics of bacterial ribosomes. Annu. Rev. Genet. 11, 297–347 (1977).

CAS  Google Scholar 

Warner, J. R. The economics of ribosome biosynthesis in yeast. Trends Biochem. Sci. 24, 437–440 (1999).

CAS  Google Scholar 

Kobayashi, T. Regulation of ribosomal RNA gene copy number and its role in modulating genome integrity and evolutionary adaptability in yeast. Cell. Mol. Life Sci. 68, 1395–1403 (2011).

CAS  Google Scholar 

Long, E. O. & Dawid, I. B. Repeated genes in eukaryotes. Annu. Rev. Biochem. 49, 727–764 (1980).

CAS  Google Scholar 

Kobayashi, T. A new role of the rDNA and nucleolus in the nucleus — rDNA instability maintains genome integrity. Bioessays 30, 267–272 (2008).

CAS  Google Scholar 

Brewer, B. J. When polymerases collide: replication and the transcriptional organization of the E. coli chromosome. Cell 53, 679–686 (1988).

CAS  Google Scholar 

Mirkin, E. V. & Mirkin, S. M. Mechanisms of transcription-replication collisions in bacteria. Mol. Cell. Biol. 25, 888–895 (2005).

CAS  Google Scholar 

Horiuchi, T., Hidaka, M. & Kobayashi, T. Termination of chromosome duplication in bacteria in Control of Cell Growth and Division (Japan Scientific Societies Press, Springer-Verlag, 1991).

Petes, T. D. Yeast ribosomal DNA genes are located on chromosome XII. Proc. Natl Acad. Sci. USA 76, 410–414 (1979).

CAS  Google Scholar 

Kobayashi, T., Heck, D. J., Nomura, M. & Horiuchi, T. 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 (1998).

CAS  Google Scholar 

Ganley, A. R. D. & Kobayashi, T. 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 (2007).

CAS  Google Scholar 

Dieci, G., Fiorino, G., Castelnuovo, M., Teichmann, M. & Pagano, A. The expanding RNA polymerase III transcriptome. Trends Genet. 23, 614–622 (2007).

CAS  Google Scholar 

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

CAS  Google Scholar 

Brewer, B. J. & Fangman, W. L. A replication fork barrier at the 3’ end of yeast ribosomal RNA genes. Cell 55, 637–643 (1988).

CAS  Google Scholar 

Linskens, M. H. & Huberman, J. A. Organization of replication of ribosomal DNA in Saccharomyces cerevisiae. Mol. Cell. Biol. 8, 4927–4935 (1988).

CAS  Google Scholar 

Brewer, B. J., Lockshon, D. & Fangman, W. L. The arrest of replication forks in the rDNA of yeast occurs independently of transcription. Cell 71, 267–276 (1992).

CAS  Google Scholar 

Kobayashi, T., Hidaka, M., Nishizawa, M. & Horiuchi, T. Identification of a site required for DNA replication fork blocking activity in the rRNA gene cluster in Saccharomyces cerevisiae. Mol. Gen. Genet. 233, 355–362 (1992).

CAS  Google Scholar 

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

CAS  Google Scholar 

Hizume, K., Endo, S., Muramatsu, S., Kobayashi, T. & Araki, H. DNA polymerase ε-dependent modulation of the pausing property of the CMG helicase at the barrier. Genes Dev. 32, 1315–1320 (2018).

CAS  Google Scholar 

Weitao, T., Budd, M. & Campbell, J. L. Evidence that yeast SGS1, DNA2, SRS2, and FOB1 interact to maintain rDNA stability. Mutat. Res. Mol. Mech. Mutagen. 532, 157–172 (2003).

CAS  Google Scholar 

Burkhalter, M. D. & Sogo, J. M. rDNA enhancer affects replication initiation and mitotic recombination: Fob1 mediates nucleolytic processing independently of replication. Mol. Cell 15, 409–421 (2004).

CAS  Google Scholar 

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 117, 441–453 (2004).

CAS  Google Scholar 

Sasaki, M. & Kobayashi, T. Ctf4 prevents genome rearrangements by suppressing DNA double-strand break formation and its end resection at arrested replication forks. Mol. Cell 66, 533–545.e5 (2017).

CAS  Google Scholar 

Kobayashi, T. & Ganley, A. R. D. Recombination regulation by transcription-induced cohesin dissociation in rDNA repeats. Science 309, 1581–1584 (2005).

CAS  Google Scholar 

Kobayashi, T., Nomura, M. & Horiuchi, T. Identification of DNA cis elements essential for expansion of ribosomal DNA repeats in Saccharomyces cerevisiae. Mol. Cell. Biol. 21, 136–147 (2001).

CAS  Google Scholar 

Santangelo, G. M., Tornow, J., McLaughlin, C. S. & Moldave, K. Properties of promoters cloned randomly from the Saccharomyces cerevisiae genome. Mol. Cell. Biol. 8, 4217–4224 (1988).

CAS  Google Scholar 

Saka, K., Ide, S., Ganley, A. R. D. & Kobayashi, T. Cellular senescence in yeast is regulated by rDNA noncoding transcription. Curr. Biol. 23, 1794–1798 (2013).

CAS  Google Scholar 

Iida, T. & Kobayashi, T. RNA polymerase I activators count and adjust ribosomal RNA gene copy number. Mol. Cell 73, 645–654 (2019).

CAS  Google Scholar 

Keener, J., Josaitis, C. A., Dodd, J. A. & Nomura, M. Reconstitution of yeast RNA polymerase I transcription in vitro from purified components. TATA-binding protein is not required for basal transcription. J. Biol. Chem. 273, 33795–33802 (1998).

CAS  Google Scholar 

Vu, L., Siddiqi, I., Lee, B. S., Josaitis, C. A. & Nomura, M. RNA polymerase switch in transcription of yeast rDNA: role of transcription factor UAF (upstream activation factor) in silencing rDNA transcription by RNA polymerase II. Proc. Natl Acad. Sci. USA 96, 4390–4395 (1999).

CAS  Google Scholar 

Florence, B. et al. Mechanism of RNA polymerase I selection by transcription factor UAF. Sci. Adv. 8, eabn5725 (2022).

Google Scholar 

Siddiqi, I. N. et al. Transcription of chromosomal rRNA genes by both RNA polymerase I and II in yeast uaf30 mutants lacking the 30 kDa subunit of transcription factor UAF. EMBO J. 20, 4512–4521 (2001).

CAS  Google Scholar 

Kulak, N. A., Pichler, G., Paron, I., Nagaraj, N. & Mann, M. Minimal, encapsulated proteomic-sample processing applied to copy-number estimation in eukaryotic cells. Nat. Methods 11, 319–324 (2014).

CAS  Google Scholar 

Iida, T. & Kobayashi, T. How do cells count multi-copy genes?: “musical chair” model for preserving the number of rDNA copies. Curr. Genet. 65, 883–885 (2019).

CAS  Google Scholar 

Sinclair, D. A. & Guarente, L. Extrachromosomal rDNA circles - A cause of aging in yeast. Cell 91, 1033–1042 (1997).

CAS  Google Scholar 

van Sluis, M. et al. Human NORs, comprising rDNA arrays and functionally conserved distal elements, are located within dynamic chromosomal regions. Genes Dev. 33, 1688–1701 (2019).

Google Scholar 

Gerber, J.-K. et al. Termination of mammalian rDNA replication: polar arrest of replication fork movement by transcription termination factor TTF-I. Cell 90, 559–567 (1997).

CAS  Google Scholar 

Akamatsu, Y. & Kobayashi, T. 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 (2015).

CAS  Google Scholar 

De Winter, R. F. & Moss, T. The ribosomal spacer in Xenopus laevis is transcribed as part of the primary ribosomal RNA. Nucleic Acids Res. 14, 6041–6051 (1986).

Google Scholar 

Kuhn, A. & Grummt, I. A novel promoter in the mouse rDNA spacer is active in vivo and in vitro. EMBO J. 6, 3487–3492 (1987).

CAS  Google Scholar 

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

CAS  Google Scholar 

Hori, Y., Shimamoto, A. & Kobayashi, T. The human ribosomal DNA array is composed of highly homogenized tandem clusters. Genome Res. 31, 1971–1982 (2021).

Google Scholar 

Parks, M. M. et al. Variant ribosomal RNA alleles are conserved and exhibit tissue-specific expression. Sci. Adv. 4, eaao0665 (2018).

Google Scholar 

Stults, D. M. et al. Human rRNA gene clusters are recombinational hotspots in cancer. Cancer Res. 69, 9096–9104 (2009).

CAS  Google Scholar 

Killen, M. W., Stults, D. M., Adachi, N., Hanakahi, L. & Pierce, A. J. Loss of Bloom syndrome protein destabilizes human gene cluster architecture. Hum. Mol. Genet. 18, 3417–3428 (2009).

CAS  Google Scholar 

Milkereit, P. & Tschochner, H. A specialized form of RNA polymerase I, essential for initiation and growth-dependent regulation of rRNA synthesis, is disrupted during transcription. EMBO J. 17, 3692–3703 (1998).

CAS  Google Scholar 

Buttgereit, D., Pflugfelder, G. & Grummt, I. Growth-dependent regulation of rRNA synthesis is mediated by a transcription initiation factor (TTF-IA). Nucleic Acids Res. 13, 8165–8180 (1985).

CAS  Google Scholar 

Yamamoto, R. T., Nogi, Y., Dodd, J. A. & Nomura, M. RRN3 gene of Saccharomyces cerevisiae encodes an essential RNA polymerase I transcription factor which interacts with the polymerase independently of DNA template. EMBO J. 15, 3964–3973 (1996).

CAS  Google Scholar 

Miller, G. et al. hRRN3 is essential in the SL1‐mediated recruitment of RNA polymerase I to rRNA gene promoters. EMBO J. 20, 1373–1382 (2001).

CAS  Google Scholar 

Moorefield, B., Greene, E. A. & Reeder, R. H. RNA polymerase I transcription factor Rrn3 is functionally conserved between yeast and human. Proc. Natl Acad. Sci. USA 97, 4724–4729 (2000).

CAS  Google Scholar 

Learned, R. M., Cordes, S. & Tjian, R. Purification and characterization of a transcription factor that confers promoter specificity to human RNA polymerase I. Mol. Cell. Biol. 5, 1358–1369 (1985).

CAS  Google Scholar 

Russell, J. & Zomerdijk, J. C. B. M. The RNA polymerase I transcription machinery. Biochem. Soc. Symp. https://doi.org/10.1042/bss0730203 (2006).

Article  Google Scholar 

Moss, T., Langlois, F., Gagnon-Kugler, T. & Stefanovsky, V. A housekeeper with power of attorney: the rRNA genes in ribosome biogenesis. Cell. Mol. Life Sci. 64, 29–49 (2007).

CAS  Google Scholar 

Keys, D. A. et al. Multiprotein transcription factor UAF interacts with the upstream element of the yeast RNA polymerase I promoter and forms a stable preinitiation complex. Genes Dev. 10, 887–903 (1996).

CAS  Google Scholar 

Vannini, A. & Cramer, P. Conservation between the RNA polymerase I, II, and III transcription initiation machineries. Mol. Cell 45, 439–446 (2012).

CAS  Google Scholar 

Miller, O. L. J. & Beatty, B. R. Visualization of nucleolar genes. Science 164, 955–957 (1969).

Google Scholar 

Lisica, A. et al. Mechanisms of backtrack recovery by RNA polymerases I and II. Proc. Natl Acad. Sci. USA 113, 2946–2951 (2016).