ArticlePLoS genetics2018
Yeast heterochromatin regulators Sir2 and Sir3 act directly at euchromatic DNA replication origins.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Replication program of a single-chromosome budding yeast strain.Nucleic acids research · 2025Article
- Genome-wide identification of the lysine deacetylases gene and its dynamic expression profile during adversity stress and infestation in Arthrinium phaeospermum.World journal of microbiology & biotechnology · 2025Article
- Mechanisms for licensing origins of DNA replication in eukaryotic cells.Nature structural & molecular biology · 2025Review
- Review
- The 80Journal of microbiology and biotechnology · 2024Article
- Where and when to start: Regulating DNA replication origin activity in eukaryotic genomes.Nucleus (Austin, Tex.) · 2023Review
- SIRT1 Prevents R-Loops during Chronological Aging by Modulating DNA Replication at rDNA Loci.Cells · 2023Article
- The increase in cell death rates in caloric restricted cells of the yeast helicase mutant rrm3 is Sir complex dependent.Scientific reports · 2023Article
- Telomere-to-Telomere genome assemblies of human-infecting Encephalitozoon species.BMC genomics · 2023Article
- Yeast ORC sumoylation status fine-tunes origin licensing.Genes & development · 2022Article
- Convergence of SIRT1 and ATR signaling to modulate replication origin dormancy.Nucleic acids research · 2022Article
- Preventing excess replication origin activation to ensure genome stability.Trends in genetics : TIG · 2022Review
- Getting there: understanding the chromosomal recruitment of the AAA+ ATPase Pch2/TRIP13 during meiosis.Current genetics · 2021Review
- Article
- Resveratrol induces H3 and H4K16 deacetylation and H2A.X phosphorylation in Toxoplasma gondii.BMC research notes · 2021Article
- Positive and Negative Regulation of DNA Replication Initiation.Trends in genetics : TIG · 2020Review
- Article
- The Rad53Nature communications · 2020Article
- Sir2 takes affirmative action to ensure equal opportunity in replication origin licensing.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Sir2 mitigates an intrinsic imbalance in origin licensing efficiency between early- and late-replicating euchromatin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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11 authors.
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Abstract
Most active DNA replication origins are found within euchromatin, while origins within heterochromatin are often inactive or inhibited. In yeast, origin activity within heterochromatin is negatively controlled by the histone H4K16 deacetylase, Sir2, and at some heterochromatic loci also by the nucleosome binding protein, Sir3. The prevailing view has been that direct functions of Sir2 and Sir3 are confined to heterochromatin. However, growth defects in yeast mutants compromised for loading the MCM helicase, such as cdc6-4, are suppressed by deletion of either SIR2 or SIR3. While these and other observations indicate that SIR2,3 can have a negative impact on at least some euchromatic origins, the genomic scale of this effect was unknown. It was also unknown whether this suppression resulted from direct functions of Sir2,3 within euchromatin, or was an indirect effect of their previously established roles within heterochromatin. Using MCM ChIP-Seq, we show that a SIR2 deletion rescued MCM complex loading at ~80% of euchromatic origins in cdc6-4 cells. Therefore, Sir2 exhibited a pervasive effect at the majority of euchromatic origins. Using MNase-H4K16ac ChIP-Seq, we show that origin-adjacent nucleosomes were depleted for H4K16 acetylation in a SIR2-dependent manner in wild type (i.e. CDC6) cells. In addition, we present evidence that both Sir2 and Sir3 bound to nucleosomes adjacent to euchromatic origins. The relative levels of each of these molecular hallmarks of yeast heterochromatin-SIR2-dependent H4K16 hypoacetylation, Sir2, and Sir3 -correlated with how strongly a SIR2 deletion suppressed the MCM loading defect in cdc6-4 cells. Finally, a screen for histone H3 and H4 mutants that could suppress the cdc6-4 growth defect identified amino acids that map to a surface of the nucleosome important for Sir3 binding. We conclude that heterochromatin proteins directly modify the local chromatin environment of euchromatic DNA replication origins.
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