<i>HPR1</i> Encodes a Global Positive Regulator of Transcription in <i>Saccharomyces cerevisiae</i>

Zhu, Yingfang; Peterson, Craig L.; Christman, Michael F.

doi:10.1128/mcb.15.3.1698

Cited by 36 publications

(47 citation statements)

References 52 publications

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“…Second, the hpr1⌬ mutation is lethal when combined with a deletion of histones H3 and H4 (hht1-hhf1⌬) (14). Consistent with these findings, overexpression of either HHT1-HHF1 or HTA-HTB (H2A-H2B) results in a severe growth defect when combined with an hpr1⌬ mutation (51). Overexpression of all four histones has no effect on the growth of an hpr1⌬ mutant strain.…”

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confidence: 67%

Role of Transcription in Plasmid Maintenance in the hpr1Δ Mutant of Saccharomyces cerevisiae

Merker

Klein

2002

Molecular and Cellular Biology

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The Saccharomyces cerevisiae hyperrecombination mutation hpr1⌬ results in instability of sequences between direct repeats that is dependent on transcription of the repeat. Here it is shown that the HPR1 gene also functions in plasmid stability in the presence of destabilizing transcription elongation. In the hpr1⌬ mutant, plasmid instability results from unchecked transcription elongation, which can be suppressed by a strong transcription terminator. The plasmid system has been used to examine in vivo aspects of transcription in the absence of Hpr1p. Nuclear run-on studies suggest that there is an increased RNA polymerase II density in the hpr1⌬ mutant strain, but this is not accompanied by an increase in accumulation of cytoplasmic mRNA. Suppression of plasmid instability in hpr1⌬ can also be achieved by high-copy expression of the RNA splicing factor SUB2, which has recently been proposed to function in mRNA export, in addition to its role in pre-mRNA splicing. High-copy-number SUB2 expression is accompanied by an increase in message accumulation from the plasmid, suggesting that the mechanism of suppression by Sub2p involves the formation of mature mRNA. Models for the role of Hpr1p in mature mRNA formation and the cause of plasmid instability in the absence of the Hpr1 protein are discussed.

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confidence: 67%

Role of Transcription in Plasmid Maintenance in the hpr1Δ Mutant of Saccharomyces cerevisiae

Merker

Klein

2002

Molecular and Cellular Biology

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“…Now we show SIN1 is known to participate in the transcriptional regulathat a short 27 amino acid peptide near the N-terminal of tion of a family of genes including HO, INO1 and the gluco-SIN1 is sufficient to bind SAP1. Taken together, these data corticoid receptor when expressed in yeast [2,4,16,17,19]. It is support the notion that SIN1 is involved in several cellular thought to primarily act as a transcriptional repressor antagfunctions, by serving as an anchor in the chromatin for moonizing the SWI/SNF complex whose function is to remodel lecules that are involved in controlling more than one process.…”

Section: Sap1 Is a Member Of The 'Aaa' Family Of Atpase Proteinssupporting

confidence: 67%

Association of yeast SAP1, a novel member of the ‘AAA’ ATPase family of proteins, with the chromatin protein SIN1

et al. 1996

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DNA in vitro [8]. Interestingly, sinl mutants are also defective Abstract The yeast SIN1 protein is a nuclear protein that together with other proteins behaves as a transcriptional in proper segregation of chromosome III but not chromosome repressor of a family of genes. In addition, sinl mutants are V during mitosis [2]. We have shown in parallel work to that defective in proper mitotic chromosome segregation. In an effort described in this paper, that the N-terminal of SIN1 is capable to understand the basis for these phenotypes, we employed the of interaction with CDC23 [9], a protein known to control yeast two-hybrid system to identify proteins that interact with chromosome segregation during mitosis [10][11][12]. SIN1 in vivo. Here, we demonstrate that SAP1, a novel protein Here we extend our previous studies to help explain the belonging to the 'AAA' family of ATPases, is able to directly biochemical basis for the disparate phenotypes of SIN1. We interact with SIN1. Furthermore, we show, using recombinant used the yeast two-hybrid system [13][14][15] as a method to molecules in vitro, that a short 27 amino acid sequence near the identify proteins that directly associate with SIN1. We demon-N-terminal of SIN1 is sufficient to bind SAP1. Previous strate that a short 27 amino acid sequence near the N-termiexperiments defined different domains of SIN that interact with other proteins and with DNA. The C-terminal domain of SIN1 nus of SIN1 is able to directly interact with a novel protein we was shown to be responsible for interaction with a protein that have termed SAP1 (SIN1 _associating protein). The predicted binds the regulatory region of HO, a gene whose transcription is amino acid sequence of SAP1 indicates that it is a member of repressed by SIN1. The central 'HMGl-like region' of SIN1 the 'AAA' (ATPase _associated with diverse cellular _activities) binds DNA, while the N-terminal of SIN1 can bind CDC23, a family of proteins. protein that regulates chromosome segregation. These data, taken together with the results presented here, suggest that SIN1 2. Materials and methods is a multifunctional chromatin protein that can interact with a number of different proteins that are involved in several different Plasmids and yeast strains cellular functions.Plasmid pBTM 116/SIN1 was constructed by subcloning the EcoRI fragment from pGEX-3X/SIN1 [16] containing the SIN1 coding re-

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“…In order to test whether there is a relationship between chromatin structure and transcriptional efficiency in hpr1 cells, we determined whether the chromatin structure of GϩC-rich sequences such as lacZ was different from that of low-GϩC-content sequences. We performed MNase sensitivity assays of the GAL1pr::lacZ fusion construct and the GAL1 endogenous genes, in which transcription was strongly and poorly impaired in hpr1 cells, respectively (11,17,67) (Fig. 9A).…”

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confidence: 99%

“…A gene linking transcription and genome instability in Saccharomyces cerevisae is HPR1, as hpr1 mutants show both increased levels of recombination between direct repeats and chromosome loss (2,49) as well as strong transcriptional defects (11,44,67). Detailed characterization of these defects has shown that the absence of Hpr1 causes impairment of transcription elongation.…”

mentioning

confidence: 99%

Hpr1 Is Preferentially Required for Transcription of Either Long or G+C-Rich DNA Sequences in Saccharomyces cerevisiae

Chávez

García-Rubio

Prado

et al. 2001

Molecular and Cellular Biology

107

131

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Hpr1 forms, together with Tho2, Mft1, and Thp2, the THO complex, which controls transcription elongation and genome stability in Saccharomyces cerevisiae. Mutations in genes encoding the THO complex confer strong transcription-impairment and hyperrecombination phenotypes in the bacterial lacZ gene. In this work we demonstrate that Hpr1 is a factor required for transcription of long as well as G؉C-rich DNA sequences. Using different lacZ segments fused to the GAL1 promoter, we show that the negative effect of lacZ sequences on transcription depends on their distance from the promoter. In parallel, we show that transcription of either a long LYS2 fragment or the S. cerevisiae YAT1 G؉C-rich open reading frame fused to the GAL1 promoter is severely impaired in hpr1 mutants, whereas transcription of LAC4, the Kluyveromyces lactis ortholog of lacZ but with a lower G؉C content, is only slightly affected. The hyperrecombination behavior of the DNA sequences studied is consistent with the transcriptional defects observed in hpr1 cells. These results indicate that both length and G؉C content are important elements influencing transcription in vivo. We discuss their relevance for the understanding of the functional role of Hpr1 and, by extension, the THO complex.The control of genome stability is essential to ensure maintenance of genetic information in all cells of a living organism. Dysfunction of this control causes mutations and chromosomal aberrations that can give rise to loss of gene function, cell death, or irreversible changes in the cell program.Genetic recombination is required for mitotic DNA repair and for proper meiotic chromosome segregation. In addition, it may also be responsible for processes of genetic instability. A number of animal diseases, including cancer, originate by events of mitotic recombination between repeats that lead to chromosomal aberrations (34). Several elements have been described to enhance mitotic recombination, including DNA damage, replication defects, alteration of chromatin structure, and transcriptional activity (reviewed in reference 3). Ikeda and Matsumoto (26) first described the influence of transcription on recombination showing that recombination of phage was stimulated by transcription. In yeast, the first example of transcription-associated recombination was the finding that a hotspot of ribosomal DNA (rDNA) recombination, HOT1, was dependent on RNA polymerase I-driven transcription (55, 60). Thomas and Rothstein (56) extended transcription-induced recombination to sequences transcribed by RNA polymerase II (RNAPII). Additional examples of RNAPII-dependent recombination have been subsequently described in yeast (21,36,50) and mammalian cells (37, 57). Special mention must be made of the modulation of recombination at the immunoglobulin loci, as both V(D)J recombination (7, 31, 38) and class switching (15) are positively controlled by transcription.A gene linking transcription and genome instability in Saccharomyces cerevisae is HPR1, as hpr1 mutants show both increased l...

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HPR1 Encodes a Global Positive Regulator of Transcription in Saccharomyces cerevisiae

Cited by 36 publications

References 52 publications

Role of Transcription in Plasmid Maintenance in the hpr1Δ Mutant of Saccharomyces cerevisiae

Role of Transcription in Plasmid Maintenance in the hpr1Δ Mutant of Saccharomyces cerevisiae

Association of yeast SAP1, a novel member of the ‘AAA’ ATPase family of proteins, with the chromatin protein SIN1

Hpr1 Is Preferentially Required for Transcription of Either Long or G+C-Rich DNA Sequences in Saccharomyces cerevisiae

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