Yeast Rtt109 Promotes Genome Stability by Acetylating Histone H3 on Lysine 56

Driscoll, Robert; Hudson, Amanda L.; Jackson, Stephen

doi:10.1126/science.1135862

Cited by 413 publications

(530 citation statements)

References 20 publications

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“…In contrast, wild-type and RTT109 FH/− C. albicans populations were homogeneous budded cells. In S. cerevisiae, inability to acetylate H3K56 leads to spontaneous DNA damage (15,16) and constitutive checkpoint activation (15), which as a result delay G2-M progression (15). We therefore suspected that constitutive DNA damage causes the aberrant morphology of C. albicans rtt109 −/− mutants.…”

Section: Resultsmentioning

confidence: 99%

“…In S. cerevisiae, H3K56 acetylation is required for replication fork stability (8,9), reassembly of chromatin after DNA damage repair, and histone association with chromatin assembly proteins (10)(11)(12)(13). A fungalspecific histone acetyl-transferase (HAT) enzyme, termed Rtt109, and its stimulatory histone chaperone cofactor, Asf1, are required for H3K56 acetylation (8,(14)(15)(16). S. cerevisiae mutants lacking Rtt109 or Asf1 display delayed cell-cycle progression (15), spontaneous DNA damage (5,17,18), unstable replication forks, and are extremely sensitive to DNA-damaging agents (8).…”

mentioning

confidence: 99%

“…A fungalspecific histone acetyl-transferase (HAT) enzyme, termed Rtt109, and its stimulatory histone chaperone cofactor, Asf1, are required for H3K56 acetylation (8,(14)(15)(16). S. cerevisiae mutants lacking Rtt109 or Asf1 display delayed cell-cycle progression (15), spontaneous DNA damage (5,17,18), unstable replication forks, and are extremely sensitive to DNA-damaging agents (8). In accordance, point mutation of H3 lysine 56 to arginine, which cannot be acetylated and mimics a positively charged, unacetylated lysine, results in similar phenotypes (5,14).…”

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Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Rosa

Boyartchuk

Zhu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

123

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Candida albicans is a ubiquitous opportunistic pathogen that is the most prevalent cause of hospital-acquired fungal infections. In mammalian hosts, C. albicans is engulfed by phagocytes that attack the pathogen with DNA-damaging reactive oxygen species (ROS). Acetylation of histone H3 lysine 56 (H3K56) by the fungal-specific histone acetyltransferase Rtt109 is important for yeast model organisms to survive DNA damage and maintain genome integrity. To assess the importance of Rtt109 for C. albicans pathogenicity, we deleted the predicted homolog of Rtt109 in the clinical C. albicans isolate, SC5314. C. albicans rtt109 −/− mutant cells lack acetylated H3K56 (H3K56ac) and are hypersensitive to genotoxic agents. Additionally, rtt109 −/− mutant cells constitutively display increased H2A S129 phosphorylation and elevated DNA repair gene expression, consistent with endogenous DNA damage. Importantly, C. albicans rtt109 −/− cells are significantly less pathogenic in mice and more susceptible to killing by macrophages in vitro than are wild-type cells. Via pharmacological inhibition of the host NADPH oxidase enzyme, we show that the increased sensitivity of rtt109 −/− cells to macrophages depends on the host's ability to generate ROS, providing a mechanistic link between the drug sensitivity, gene expression, and pathogenesis phenotypes. We conclude that Rtt109 is particularly important for fungal pathogenicity, suggesting a unique target for therapeutic antifungal compounds.acetylation | chromatin | fungal pathogenesis | DNA damage resistance | macrophage

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Rosa

Boyartchuk

Zhu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

123

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“…There is indirect evidence that Spt10 might acetylate H3-K56 at the histone gene promoters (Xu et al 2005), but it has been shown since that Rtt109 is the HAT responsible for most, if not all, H3-K56 acetylation in yeast (Driscoll et al 2007;Han et al 2007). …”

Section: Cell-cycle-dependent Activation Of the Histone Genesmentioning

confidence: 99%

Regulation of Histone Gene Expression in Budding Yeast

Eriksson¹,

Ganguli²,

Nagarajavel³

et al. 2012

Genetics

116

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We discuss the regulation of the histone genes of the budding yeast Saccharomyces cerevisiae. These include genes encoding the major core histones (H3, H4, H2A, and H2B), histone H1 (HHO1), H2AZ (HTZ1), and centromeric H3 (CSE4). Histone production is regulated during the cell cycle because the cell must replicate both its DNA during S phase and its chromatin. Consequently, the histone genes are activated in late G1 to provide sufficient core histones to assemble the replicated genome into chromatin. The major core histone genes are subject to both positive and negative regulation. The primary control system is positive, mediated by the histone gene-specific transcription activator, Spt10, through the histone upstream activating sequences (UAS) elements, with help from the major G1/S-phase activators, SBF (Swi4 cell cycle box binding factor) and perhaps MBF (MluI cell cycle box binding factor). Spt10 binds specifically to the histone UAS elements and contains a putative histone acetyltransferase domain. The negative system involves negative regulatory elements in the histone promoters, the RSC chromatin-remodeling complex, various histone chaperones [the histone regulatory (HIR) complex, Asf1, and Rtt106], and putative sequence-specific factors. The SWI/SNF chromatin-remodeling complex links the positive and negative systems. We propose that the negative system is a damping system that modulates the amount of transcription activated by Spt10 and SBF. We hypothesize that the negative system mediates negative feedback on the histone genes by histone proteins through the level of saturation of histone chaperones with histone. Thus, the negative system could communicate the degree of nucleosome assembly during DNA replication and the need to shut down the activating system under replication-stress conditions. We also discuss post-transcriptional regulation and dosage compensation of the histone genes.

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“…For instance, Hat1 acetylates lysine 5 and 12 of H4 (Ai and Parthun, 2004). Rtt109 acetylates lysine 56 of H3 in yeast (Driscoll et al, 2007;Han et al, 2007), and in mammalian cells, this modification is catalyzed by CBP/p300 and/or Gcn5 (Das et al, 2009;Tjeertes et al, 2009). Recently, we have shown that new H3 acetylation at the N-terminal tail is carried out by the lysine acetyltransferases Gcn5, Rtt109 and possibly Elp3 (Li et al, 2009;Burgess et al, 2010).…”

Section: Multiple Acetylation Events Regulate Assembly Of Newly-synthmentioning

confidence: 99%

Histones, histone chaperones and nucleosome assembly

Burgess

Zhang

2010

Protein Cell

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Chromatin structure governs a number of cellular processes including DNA replication, transcription, and DNA repair. During DNA replication, chromatin structure including the basic repeating unit of chromatin, the nucleosome, is temporarily disrupted, and then reformed immediately after the passage of the replication fork. This coordinated process of nucleosome assembly during DNA replication is termed replication-coupled nucleosome assembly. Disruption of this process can lead to genome instability, a hallmark of cancer cells. Therefore, addressing how replication-coupled nucleosome assembly is regulated has been of great interest. Here, we review the current status of this growing field of interest, highlighting recent advances in understanding the regulation of this important process by the dynamic interplay of histone chaperones and histone modifications.

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Yeast Rtt109 Promotes Genome Stability by Acetylating Histone H3 on Lysine 56

Cited by 413 publications

References 20 publications

Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Regulation of Histone Gene Expression in Budding Yeast

Histones, histone chaperones and nucleosome assembly

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