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PLoS Genet. 2019 May 13;15(5):e1008138. doi: 10.1371/journal.pgen.1008138. eCollection 2019 May.

Sir2 suppresses transcription-mediated displacement of Mcm2-7 replicative helicases at the ribosomal DNA repeats.

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Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, United States of America.
Department of Medicine, University of Washington, Seattle, WA, United States of America.
Department of Biochemistry, University of Washington, Seattle, WA, United States of America.


Repetitive DNA sequences within eukaryotic heterochromatin are poorly transcribed and replicate late in S-phase. In Saccharomyces cerevisiae, the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA arrays (rDNA). Despite the widespread association between transcription and replication timing, it remains unclear how transcription might impinge on replication, or vice versa. Here we show that, when silencing of an RNA polymerase II (RNA Pol II)-transcribed non-coding RNA at the rDNA is disrupted by SIR2 deletion, RNA polymerase pushes and thereby relocalizes replicative Mcm2-7 helicases away from their loading sites to an adjacent region with low nucleosome occupancy, and this relocalization is associated with increased rDNA origin efficiency. Our results suggest a model in which two of the major defining features of heterochromatin, transcriptional silencing and late replication, are mechanistically linked through suppression of polymerase-mediated displacement of replication initiation complexes.

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Conflict of interest statement

The authors have declared that no competing interests exist.

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