ArticleGenetics2008
Histone H3 K56 hyperacetylation perturbs replisomes and causes DNA damage.
Article in Genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 74 citations in OpenAlex.
- Chromatin architecture sets origin licensing capacity.Research square · 2026Article
- Chromatin architecture sets origin licensing capacity.bioRxiv : the preprint server for biology · 2026Article
- Article
- Mechanism of Histone Arginine Methylation Dynamic Change in Cellular Stress.International journal of molecular sciences · 2024Article
- Genetic inhibitors of APOBEC3B-induced mutagenesis.Genome research · 2023Article
- Persistent Acetylation of Histone H3 Lysine 56 Compromises the Activity of DNA Replication Origins.Molecular and cellular biology · 2023Article
- Article
- Review
- Effects of sirtuins on the riboflavin production in Ashbya gossypii.Applied microbiology and biotechnology · 2021Article
- Histones on fire: the effect of Dun1 and Mrc1 on origin firing and replication of hyper-acetylated genomes.Current genetics · 2021Review
- Genetic-variant hotspots and hotspot clusters in the human genome facilitating adaptation while increasing instability.Human genomics · 2021Article
- Review
- Gene repression in S. cerevisiae-looking beyond Sir-dependent gene silencing.Current genetics · 2021Review
- A novel role for Dun1 in the regulation of origin firing upon hyper-acetylation of H3K56.PLoS genetics · 2021Article
- Genetic interaction mapping informs integrative structure determination of protein complexes.Science (New York, N.Y.) · 2020Article
- Yeast Sirtuin Family Members Maintain Transcription Homeostasis to Ensure Genome Stability.Cell reports · 2019Article
- A synthetic non-histone substrate to study substrate targeting by the Gcn5 HAT and sirtuin HDACs.The Journal of biological chemistry · 2019Article
- How DoesFrontiers in microbiology · 2019Article
- Fission Yeast Sirtuin Hst4 Functions in Preserving Genomic Integrity by Regulating Replisome Component Mcl1.Scientific reports · 2018Article
- An interplay between multiple sirtuins promotes completion of DNA replication in cells with short telomeres.PLoS genetics · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Deacetylation of histone H3 K56, regulated by the sirtuins Hst3p and Hst4p, is critical for maintenance of genomic stability. However, the physiological consequences of a lack of H3 K56 deacetylation are poorly understood. Here we show that cells lacking Hst3p and Hst4p, in which H3 K56 is constitutively hyperacetylated, exhibit hallmarks of spontaneous DNA damage, such as activation of the checkpoint kinase Rad53p and upregulation of DNA-damage inducible genes. Consistently, hst3 hst4 cells display synthetic lethality interactions with mutations that cripple genes involved in DNA replication and DNA double-strand break (DSB) repair. In most cases, synthetic lethality depends upon hyperacetylation of H3 K56 because it can be suppressed by mutation of K56 to arginine, which mimics the nonacetylated state. We also show that hst3 hst4 phenotypes can be suppressed by overexpression of the PCNA clamp loader large subunit, Rfc1p, and by inactivation of the alternative clamp loaders CTF18, RAD24, and ELG1. Loss of CTF4, encoding a replisome component involved in sister chromatid cohesion, also suppresses hst3 hst4 phenotypes. Genetic analysis suggests that CTF4 is a part of the K56 acetylation pathway that converges on and modulates replisome function. This pathway represents an important mechanism for maintenance of genomic stability and depends upon proper regulation of H3 K56 acetylation by Hst3p and Hst4p. Our data also suggest the existence of a precarious balance between Rfc1p and the other RFC complexes and that the nonreplicative forms of RFC are strongly deleterious to cells that have genomewide and constitutive H3 K56 hyperacetylation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.