Histone H3 Thr 45 phosphorylation is a replication-associated post-translational modification in S. cerevisiae

Baker, Stephen P.; Phillips, J. D.; Anderson, Scott; Qiu, Qinghua; Shabanowitz, Jeffrey; Smith, M. Mitchell; Yates, John R.; Hunt, Donald F.; Grant, Patrick A.

doi:10.1038/ncb2030

Cited by 78 publications

(89 citation statements)

References 32 publications

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“…Thr45 has also been reported to be phosphorylated in budding yeast by the kinase Cdc7-Dbf4. This modification has been related to proper replication of DNA in budding yeast (5). Another significant C-terminal modification is H3 Tyr41 phosphorylation.…”

Section: Histone H3mentioning

confidence: 99%

A Peek into the Complex Realm of Histone Phosphorylation

Banerjee

Chakravarti

2011

Molecular and Cellular Biology

170

111

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Although discovered long ago, posttranslational phosphorylation of histones has been in the spotlight only recently. Information is accumulating almost daily on phosphorylation of histones and their roles in cellular physiology and human diseases. An extensive cross talk exists between phosphorylation and other posttranslational modifications, which together regulate various biological processes, including gene transcription, DNA repair, and cell cycle progression. Recent research on histone phosphorylation has demonstrated that nearly all histone types are phosphorylated at specific residues and that these modifications act as a critical intermediate step in chromosome condensation during cell division, transcriptional regulation, and DNA damage repair. As with all young fields, apparently conflicting and sometimes controversial observations about histone phosphorylations and their true functions in different species are found in the literature. Accumulating evidence suggests that instead of functioning strictly as part of a general code, histone phosphorylation probably functions by establishing cross talk with other histone modifications and serving as a platform for recruitment or release of effector proteins, leading to a downstream cascade of events. Here we extensively review published information on the complexities of histone phosphorylation, the roles of proteins recognizing these modifications and the resuting physiological outcome, and, importantly, future challenges and opportunities in this fast-moving field.To fit the enormous length of the eukaryotic genome into the nucleus of a tiny cell requires some very sophisticated packaging. But this packaging must also be highly flexible and malleable so that the genome can be correctly replicated, transcribed, and finally translated. To meet these requirements, DNA is organized in a higher-order nucleoprotein complex known as chromatin. The basic unit of chromatin is the nucleosome, which is essentially DNA wrapped around a core of histone proteins. Each nucleosome is made up of an octamer of core histones (two each of H2A, H2B, H3, and H4), and around this histone core, the DNA is wrapped in two superhelical turns of 147 bp (67). Nucleosomes are spaced at intervals and linked by 20 to 60 bp of linker DNA to form an approximately 10-nm "beads on a string" structure, with H1 linker histones contacting the exit and entry points of the DNA strand that is spooled onto each nucleosome (141). Structurally, histones can be divided into the core domain, which makes up approximately 75% of the protein and is composed of histone fold motifs that physically interact with themselves to form the H2A/2B and H3/4 heterodimers, and the flexible tail domain, which makes up the remaining 25% of the protein.The tail domain is structurally undefined but has been found to be highly conserved. The tail domains are located at the amino termini of the four histones and the carboxyl terminus of H2A and are generally defined by their sensitivity to proteases.Nucleosomes are belie...

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Section: Histone H3mentioning

confidence: 99%

A Peek into the Complex Realm of Histone Phosphorylation

Banerjee

Chakravarti

2011

Molecular and Cellular Biology

170

111

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“…Histone H3-S28ph is linked to H3-S10ph and is associated with transcriptional response to stress in mammalian cells (Clayton and Mahadevan 2003;. Histone H3-T45ph functions during DNA replication (Baker et al 2010), and, lastly, H2A-S121ph has a role in DNA damage and protection of centromeric cohesion in budding yeast (Fernius and Hardwick 2007;Moore et al 2007). …”

Section: Does Rts1 Suppression Require Specific Histone Residues?mentioning

confidence: 99%

Promotion of Cell Viability and Histone Gene Expression by the Acetyltransferase Gcn5 and the Protein Phosphatase PP2A in Saccharomyces cerevisiae

et al. 2016

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Histone modifications direct chromatin-templated events in the genome and regulate access to DNA sequence information. There are multiple types of modifications, and a common feature is their dynamic nature. An essential step for understanding their regulation, therefore, lies in characterizing the enzymes responsible for adding and removing histone modifications. Starting with a dosagesuppressor screen in Saccharomyces cerevisiae, we have discovered a functional interaction between the acetyltransferase Gcn5 and the protein phosphatase 2A (PP2A) complex, two factors that regulate post-translational modifications. We find that RTS1, one of two genes encoding PP2A regulatory subunits, is a robust and specific high-copy suppressor of temperature sensitivity of gcn5D and a subset of other gcn5D phenotypes. Conversely, loss of both PP2A Rts1 and Gcn5 function in the SAGA and SLIK/SALSA complexes is lethal. RTS1 does not restore global transcriptional defects in gcn5D; however, histone gene expression is restored, suggesting that the mechanism of RTS1 rescue includes restoration of specific cell cycle transcripts. Pointing to new mechanisms of acetylation-phosphorylation cross-talk, RTS1 high-copy rescue of gcn5D growth requires two residues of H2B that are phosphorylated in human cells. These data highlight the potential significance of dynamic phosphorylation and dephosphorylation of these deeply conserved histone residues for cell viability. KEYWORDS chromatin; transcription; phosphorylation; acetylation (IOC2, PAB1, RHO2, MED6, ZDS1, PP2A B56 ) A T the foundation of nuclear DNA organization in eukaryotes is the dynamic formation, movement, and modification of nucleosomes. Acetylation and phosphorylation are two histone post-translational modifications (PTMs) catalyzed by histone acetyltransferases (HATs) and kinases and reversed by histone deacetylases (HDACs) and phosphatases that alter nucleosome structure and function. Tightly regulated acetylation and phosphorylation of specific histone residues have deeply conserved functions in eukaryotes that are critical for transcriptional regulation, replication, repair, and segregation of eukaryotic genomes (Banerjee and Chakravarti 2011;Rossetto et al. 2012;Tessarz and Kouzarides 2014).One well-conserved HAT is Gcn5, which specifically targets histones H3 and H2B as part of multiple complexes (Grant et al. 1997;Eberharter et al. 1999;Grant et al. 1999;Howe et al. 2001;Sterner et al. 2002;Pray-Grant et al. 2005). Gcn5 is a key regulator of eukaryotic gene expression and acetylates H3 at promoters of active genes (Pokholok et al. 2005;Nagy and Tora 2007;Rosaleny et al. 2007). Its role as a transcriptional activator is so fundamental that Gcn5 is essential in most eukaryotes studied. An exception of note is budding yeast, where deletion of GCN5 is tolerated, but does cause a spectrum of phenotypes, including defects in gene activation, particularly for stress-regulated genes, and altered cell cycle progression (Howe et al. 2001;Huisinga and Pugh 2004;Vernarecci ...

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“…Phosphorylation of H3 Thr45 is mediated by the kinase Cdc7-Dbf4. It has been shown that Thr45 phosphorylation peaks during DNA replication and that the loss of this phosphorylation site causes phenotypes consistent with replicative defects (Baker et al, 2010).  Topoisomerase Top2 cleavage and re-sealing of the phosphodiester backbone is required for replication and recombination processes.…”

Section: Post-translational Modificationsmentioning

confidence: 99%

The Relationship Between Replication and Recombination

Zavec¹

2011

DNA Replication and Related Cellular Processes

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Histone H3 Thr 45 phosphorylation is a replication-associated post-translational modification in S. cerevisiae

Cited by 78 publications

References 32 publications

A Peek into the Complex Realm of Histone Phosphorylation

A Peek into the Complex Realm of Histone Phosphorylation

Promotion of Cell Viability and Histone Gene Expression by the Acetyltransferase Gcn5 and the Protein Phosphatase PP2A in Saccharomyces cerevisiae

The Relationship Between Replication and Recombination

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