CDC68, a yeast gene that affects regulation of cell proliferation and transcription, encodes a protein with a highly acidic carboxyl terminus.

Rowley, Adele; Singer, Richard A.; Johnston, Gerald C.

doi:10.1128/mcb.11.11.5718

Cited by 122 publications

(132 citation statements)

References 64 publications

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“…FACT activity is perturbed when nucleosomes are covalently cross-linked, and FACT physically interacts with both nucleosomes and H2A/H2B dimers (Orphanides et al 1999;Belotserkovskaya et al 2003). Moreover, in yeast, mutations in histone H4 that disrupt associations with H2A/H2B dimers exhibit phenotypes similar to those of Spt16 mutant strains (Malone et al 1991;Rowley et al 1991;Santisteban et al 1997). Notably, FACT was shown to facilitate the loss of H2A/H2B dimers in assays using immobilized nucleosomal templates (Belotserkovskaya et al 2003).…”

Section: Genes and Development 2447mentioning

confidence: 84%

“…Genetic studies in yeast had identified the later recognized subunits of FACT as having a role in productive elongation through chromatin. The yeast FACT components, Spt16/Cdc68 and Pob3, are encoded by essential genes and are implicated in the regulation of transcription and chromatin structure, as well as the proper progression though the cell cycle (Malone et al 1991;Rowley et al 1991;Xu et al 1993;Lycan et al 1994). Interestingly, studies to identify factors involved in DNA replication in yeast isolated the small subunit of FACT, Pob3, as a polypeptide that bound the catalytic subunit of DNA polymerase alpha (Wittmeyer and Formosa 1997).…”

Section: Genes and Development 2447mentioning

confidence: 99%

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Elongation by RNA polymerase II: the short and long of it

Sims¹,

Belotserkovskaya²,

Reinberg³

2004

Genes Dev.

617

586

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Appreciable advances into the process of transcript elongation by RNA polymerase II (RNAP II) have identified this stage as a dynamic and highly regulated step of the transcription cycle. Here, we discuss the many factors that regulate the elongation stage of transcription. Our discussion includes the classical elongation factors that modulate the activity of RNAP II, and the more recently identified factors that facilitate elongation on chromatin templates. Additionally, we discuss the factors that associate with RNAP II, but do not modulate its catalytic activity. Elongation is highlighted as a central process that coordinates multiple stages in mRNA biogenesis and maturation.The regulation of gene expression is one of the most intensely studied areas in all of science. Differential gene expression in multicellular organisms forms the foundation of cell-type specificity. Deregulation of the appropriate pattern of gene expression has profound effects on cellular function and underlies many diseases. Although there are many cellular processes that control gene expression, the most direct regulation occurs during transcription. The transcription of protein-coding genes in eukaryotes is performed by RNA polymerase II (RNAP II). Up until recently, the vast majority of studies aimed at elucidating the molecular mechanisms of transcription regulation have focused on early stages, such as the formation of a transcription initiation complex (preinitiation) and initiation (see below). For many years, transcript elongation has been thought of as the trivial addition of ribonucleoside triphosphates to the growing mRNA chain. It is now apparent that this process is a dynamic and highly regulated stage of the transcription cycle capable of coordinating downstream events. Numerous factors have been identified that specifically target the elongation stage of transcription. Importantly, multiple steps in mRNA maturation, including premRNA capping, splicing, 3Ј-end processing, surveillance, and export, are modulated through interactions with the RNAP II transcript elongation complex (TEC). It also appears that distinct elongation factors function in specific transcriptional contexts; the requirements for these specialized factors are largely unknown and highlight the need to better understand elongation in vivo. Many molecular and biochemical approaches have been used to quantify the different aspects of elongation, many of which are discussed below. It remains important to assimilate both in vitro and in vivo experimental systems when discussing what constitutes an elongation factor. An elongation factor can be defined as any molecule that affects the activities of or is associated with the TEC. We suggest that there are at least two major types of transcript elongation factors: one family, referred to as active elongation factors, and a second family, denoted as passive elongation factors. The difference resides in whether the factor affects the catalytic activity of RNAP II, regardless of whether the factor remains associate...

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Section: Genes and Development 2447mentioning

confidence: 84%

Section: Genes and Development 2447mentioning

confidence: 99%

Elongation by RNA polymerase II: the short and long of it

Sims¹,

Belotserkovskaya²,

Reinberg³

2004

Genes Dev.

617

586

View full text Add to dashboard Cite

show abstract

“…Consistent with a nucleosome assembly function, FACT has been implicated in the deposition of new nucleosomes after DNA replication (Belotserkovskaya et al 2003;Vandemark et al 2006) as well as in the reestablishment of repressive chromatin after transcription (Jamai et al 2009). Defects in this nucleosome deposition activity are likely to be the cause of cryptic promoter activation (Kaplan et al 2003), failed repression of SER3 expression (Hainer et al 2010), and the Spt 2 phenotype (Malone et al 1991;Rowley et al 1991). Most FACT gene mutations (including spt16-11) cause phenotypes associated with chromatin quality defects, indicating that maintaining appropriately repressive chromatin throughout the genome requires optimal levels of FACT activity.…”

Section: Discussionmentioning

confidence: 99%

Insight Into the Mechanism of Nucleosome Reorganization From Histone Mutants That Suppress Defects in the FACT Histone Chaperone

et al. 2011

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FACT (FAcilitates Chromatin Transcription/Transactions) plays a central role in transcription and replication in eukaryotes by both establishing and overcoming the repressive properties of chromatin. FACT promotes these opposing goals by interconverting nucleosomes between the canonical form and a more open reorganized form. In the forward direction, reorganization destabilizes nucleosomes, while the reverse reaction promotes nucleosome assembly. Nucleosome destabilization involves disrupting contacts among histone H2A-H2B dimers, (H3-H4) 2 tetramers, and DNA. Here we show that mutations that weaken the dimer:tetramer interface in nucleosomes suppress defects caused by FACT deficiency in vivo in the yeast Saccharomyces cerevisiae. Mutating the gene that encodes the Spt16 subunit of FACT causes phenotypes associated with defects in transcription and replication, and we identify histone mutants that selectively suppress those associated with replication. Analysis of purified components suggests that the defective version of FACT is unable to maintain the reorganized nucleosome state efficiently, whereas nucleosomes with mutant histones are reorganized more easily than normal. The genetic suppression observed when the FACT defect is combined with the histone defect therefore reveals the importance of the dynamic reorganization of contacts within nucleosomes to the function of FACT in vivo, especially to FACT's apparent role in promoting progression of DNA replication complexes. We also show that an H2B mutation causes different phenotypes, depending on which of the two similar genes that encode this protein are altered, revealing unexpected functional differences between these duplicated genes and calling into question the practice of examining the effects of histone mutants by expressing them from a single plasmid-borne allele.

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“…Interestingly, a large number of these genes encode or associate with components of Ccr4-Not complexes (e.g., CCR4, PAF1, HPR1, CAF1, and others) ( Jorgensen et al 2002;Zhang et al 2002). While data indicate that loss of function of a number of gene products associated with Ccr4 (e.g., paf1, ctr9, cdc73, and cdc68) alters G 1 -phase cyclin expression, a similar function for Ccr4 has not yet been identified (Reed et al 1988;Rowley et al 1991;Chang et al 1999;Koch et al 1999;Porter et al 2002). On the basis of these observations and the similarity between the large-cell phenotype of ccr4D cells and cln3D or bck2D cells, the goal of this work was to test the hypothesis that Ccr4 modulates cell size by regulating CLN1 and CLN2 expression.…”

mentioning

confidence: 96%

Ccr4 Alters Cell Size in Yeast by Modulating the Timing of CLN1 and CLN2 Expression

Manukyan

Zhang²,

Thippeswamy

et al. 2008

Genetics

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Large, multisubunit Ccr4-Not complexes are evolutionarily conserved global regulators of gene expression. Deletion of CCR4 or several components of Ccr4-Not complexes results in abnormally large cells. Since yeast must attain a critical cell size at Start to commit to division, the large size of ccr4D cells implies that they may have a size-specific proliferation defect. Overexpression of CLN1, CLN2, CLN3, and SWI4 reduces the size of ccr4D cells, suggesting that ccr4D cells have a G 1 -phase cyclin deficiency. In support of this, we find that CLN1 and CLN2 expression and budding are delayed in ccr4D cells. Moreover, overexpression of CCR4 advances the timing of CLN1 expression, promotes premature budding, and reduces cell size. Genetic analyses suggest that Ccr4 functions independently of Cln3 and downstream of Bck2. Thus, like cln3Dbck2D double deletions, cln3Dccr4D cells are also inviable. However, deletion of Whi5, a transcriptional repressor of CLN1 and CLN2, restores viability. We find that Ccr4 negatively regulates the half-life of WHI5 mRNAs, and we conclude that, by modulating the stability of WHI5 mRNAs, Ccr4 influences the size-dependent timing of G 1 -phase cyclin transcription.

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CDC68, a yeast gene that affects regulation of cell proliferation and transcription, encodes a protein with a highly acidic carboxyl terminus.

Cited by 122 publications

References 64 publications

Elongation by RNA polymerase II: the short and long of it

Elongation by RNA polymerase II: the short and long of it

Insight Into the Mechanism of Nucleosome Reorganization From Histone Mutants That Suppress Defects in the FACT Histone Chaperone

Ccr4 Alters Cell Size in Yeast by Modulating the Timing of CLN1 and CLN2 Expression

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