CDC28 phosphorylates Cac1p and regulates the association of chromatin assembly factor i with chromatin

Jeffery, Daniel; Kakusho, Naoko; You, Zhiying; Gharib, Marlène; Wyse, Brandon A.; Drury, Erin; Weinreich, Michael; Thibault, Pierre; Verreault, Alain; Masai, Hisao; Yankulov, Krassimir

doi:10.4161/15384101.2014.973745

Cited by 18 publications

(41 citation statements)

References 49 publications

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“…Once recruited to the replication fork by PCNA, CAF-1 receives H3–H4 dimers from the histone chaperone ASF1 and deposits them onto DNA to form a DNA-(H3–H4) 2 complex known as the tetrasome, thereby initiating nucleosome assembly ( 37 ) (Figure 1 ). In addition to recruitment by PCNA, coordination of CAF-1 activity with DNA replication is further regulated by CDK-dependent phosphorylation of the p150 and p60 subunits of CAF-1 ( 38 , 39 ). Importantly, CAF-1 also forms a distinct complex with the essential replication kinase Cdc7-Dbf4 in vivo , suggesting that CAF-1 activity is regulated throughout the cell cycle by phosphorylation ( 40 ).…”

Section: Introductionmentioning

confidence: 99%

Mechanistic insights into histone deposition and nucleosome assembly by the chromatin assembly factor-1

Sauer

Liu

et al. 2018

Nucleic Acids Research

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Eukaryotic chromatin is a highly dynamic structure with essential roles in virtually all DNA-dependent cellular processes. Nucleosomes are a barrier to DNA access, and during DNA replication, they are disassembled ahead of the replication machinery (the replisome) and reassembled following its passage. The Histone chaperone Chromatin Assembly Factor-1 (CAF-1) interacts with the replisome and deposits H3–H4 directly onto newly synthesized DNA. Therefore, CAF-1 is important for the establishment and propagation of chromatin structure. The molecular mechanism by which CAF-1 mediates H3–H4 deposition has remained unclear. However, recent studies have revealed new insights into the architecture and stoichiometry of the trimeric CAF-1 complex and how it interacts with and deposits H3–H4 onto substrate DNA. The CAF-1 trimer binds to a single H3–H4 dimer, which induces a conformational rearrangement in CAF-1 promoting its interaction with substrate DNA. Two CAF-1•H3–H4 complexes co-associate on nucleosome-free DNA depositing (H3–H4)2 tetramers in the first step of nucleosome assembly. Here, we review the progress made in our understanding of CAF-1 structure, mechanism of action, and how CAF-1 contributes to chromatin dynamics during DNA replication.

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Section: Introductionmentioning

confidence: 99%

Mechanistic insights into histone deposition and nucleosome assembly by the chromatin assembly factor-1

Sauer

Liu

et al. 2018

Nucleic Acids Research

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“…Conversely, the interpretation of in vivo data is confounded by the complexity and cross-connections of the global signaling network, in which perturbation of a single kinase can alter phosphorylation not only of cognate direct substrates but also through indirect effects on many other substrates that may reside in distant regions of the network. Due to these difficulties, the identification of direct kinase substrates requires both in vivo and in vitro studies with multiple levels of cross-validation that is time consuming and often not comprehensive (11,12).…”

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confidence: 99%

Machine Learning of Global Phosphoproteomic Profiles Enables Discrimination of Direct versus Indirect Kinase Substrates

Kanshin

Giguère

Cheng

et al. 2017

Molecular & Cellular Proteomics

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Mass spectrometry allows quantification of tens of thousands of phosphorylation sites from minute amounts of cellular material. Despite this wealth of information, our understanding of phosphorylation-based signaling is limited, in part because it is not possible to deconvolute substrate phosphorylation that is directly mediated by a particular kinase phosphorylation that is mediated by downstream kinases. Here, we describe a framework for assignment of direct kinase substrates using a combination of selective chemical inhibition, quantitative phosphoproteomics, and machine learning techniques. Our workflow allows classification of phosphorylation events following inhibition of an analog-sensitive kinase into kinase-independent effects of the inhibitor, direct effects on cognate substrates, and indirect effects mediated by downstream kinases or phosphatases. We applied this method to identify many direct targets of Cdc28 and Snf1 kinases in the budding yeast Global phosphoproteome analysis of acute time-series demonstrated that dephosphorylation of direct kinase substrates occurs more rapidly compared with indirect substrates, both after inhibitor treatment and under a physiological nutrient shift in cells. Mutagenesis experiments revealed a high proportion of functionally relevant phosphorylation sites on Snf1 targets. For example, Snf1 itself was inhibited through autophosphorylation on Ser and new phosphosites were discovered that modulate the activity of the Reg1 regulatory subunit of the Glc7 phosphatase and the Gal83 β-subunit of SNF1 complex. This methodology applies to any kinase for which a functional analog sensitive version can be constructed to facilitate the dissection of the global phosphorylation network.

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“…Our earlier studies concur with these findings and indicate that the epigenetic phenotypes in cac1D and rrm3D should not be attributed to the PCNA-PIP interactions alone. 42 Together, our observations suggest a complex PCNA-based control at replication forks. We need to consider that more than one PCNA ring can operate at the lagging strand and that PCNA can partner with different proteins at the lagging and the leading strands.…”

Section: Interactions Between Pcna Rrm3p and Caf-imentioning

confidence: 55%

RRM3regulates epigenetic conversions inSaccharomyces cerevisiaein conjunction with Chromatin Assembly Factor I

Wyse

Oshidari

Rowlands

et al. 2016

Nucleus

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Chromatin structures are transmitted to daughter cells through a complex system of nucleosome disassembly and re-assembly at the advancing replication forks. However, the role of replication pausing in the transmission and perturbation of chromatin structures has not been addressed. RRM3 encodes a DNA helicase, which facilitates replication at sites covered with non-histone protein complexes (tRNA genes, active gene promoters, telomeres) in Saccharomyces cerevisiae. In this report we show that the deletion of RRM3 reduces the frequency of epigenetic conversions in the subtelomeric regions of the chromosomes. This phenotype is strongly dependent on 2 histone chaperones, CAF-I and ASF1, which are involved in the reassembly of nucleosomes behind replication forks, but not on the histone chaperone HIR1. We also show that the deletion of RRM3 increases the spontaneous mutation rates in conjunction with CAF-I and ASF1, but not HIR1. Finally, we demonstrate that Rrm3p and CAF-I compete for the binding to the DNA replication clamp PCNA (Proliferating Cell Nuclear Antigen). We propose that the stalling of DNA replication predisposes to epigenetic conversions and that RRM3 and CAF-I play key roles in this process.

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CDC28 phosphorylates Cac1p and regulates the association of chromatin assembly factor i with chromatin

Cited by 18 publications

References 49 publications

Mechanistic insights into histone deposition and nucleosome assembly by the chromatin assembly factor-1

Mechanistic insights into histone deposition and nucleosome assembly by the chromatin assembly factor-1

Machine Learning of Global Phosphoproteomic Profiles Enables Discrimination of Direct versus Indirect Kinase Substrates

RRM3regulates epigenetic conversions inSaccharomyces cerevisiaein conjunction with Chromatin Assembly Factor I

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