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. 2025 Oct 27.
doi: 10.1002/1873-3468.70193. Online ahead of print.

Rad27/FEN1 prevents accumulation of Okazaki fragments and ribosomal DNA copy number changes

Tsugumi Yamaji  1 , Yuko Katayama  1 , Nanase Arata  1 , Mariko Sasaki  1   2
Affiliations

Rad27/FEN1 prevents accumulation of Okazaki fragments and ribosomal DNA copy number changes

Tsugumi Yamaji et al. FEBS Lett. .

Abstract

DNA copy number changes are the most frequent genomic alterations in cancer cells. Here, we demonstrate that Rad27/FEN1, a structure-specific nuclease in budding yeast, plays a crucial role in maintaining the stability of the ribosomal DNA (rDNA) repeats. Severe rDNA instability is observed in the rad27∆ mutant, independently of Fob1-mediated DNA replication fork arrest and DNA double-strand break (DSB) formation in the rDNA. The rad27Δ mutant accumulates Okazaki fragments in the rDNA region, without inducing the formation of detectable DSBs. Similar rDNA instability is observed in DNA ligaseCdc9-deficient cells. Furthermore, Exonuclease 1 and PCNA partially compensate for the loss of Rad27 in rDNA stabilization. These findings highlight the importance of proper Okazaki fragment maturation in the maintenance of rDNA stability.

Keywords: DNA copy number changes; Okazaki fragment; Rad27; genome instability; rDNA instability; single‐strand break.

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References

    1. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M et al. (2010) The landscape of somatic copy‐number alteration across human cancers. Nature 463, 899–905.
    1. Rendo V, Schubert M, Khuu N, Suarez Peredo Rodriguez MF, Whyte D, Ling X, van den Brink A, Huang K, Swift M, He Y et al. (2025) A compendium of amplification‐related gain of sensitivity genes in human cancer. Nat Commun 16, 1077.
    1. Ben‐David U and Amon A (2020) Context is everything: aneuploidy in cancer. Nat Rev Genet 21, 44–62.
    1. Hastings PJ, Lupski JR, Rosenberg SM and Ira G (2009) Mechanisms of change in gene copy number. Nat Rev Genet 10, 551–564.
    1. Sasaki M, Lange J and Keeney S (2010) Genome destabilization by homologous recombination in the germ line. Nat Rev Mol Cell Biol 11, 182–195.

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