HPR1

Summary

Gene Symbol: HPR1
Description: Hpr1p
Alias: TRF1, Hpr1p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Huertas P, García Rubio M, Wellinger R, Luna R, Aguilera A. An hpr1 point mutation that impairs transcription and mRNP biogenesis without increasing recombination. Mol Cell Biol. 2006;26:7451-65 pubmed
    ..To get more insight into the interconnection between mRNP biogenesis and genomic instability, we searched for HPR1 mutations that differentially affect gene expression and recombination...
  2. Schneiter R, Guerra C, Lampl M, Gogg G, Kohlwein S, Klein H. The Saccharomyces cerevisiae hyperrecombination mutant hpr1Delta is synthetically lethal with two conditional alleles of the acetyl coenzyme A carboxylase gene and causes a defect in nuclear export of polyadenylated RNA. Mol Cell Biol. 1999;19:3415-22 pubmed
  3. Rondon A, Garcia Rubio M, González Barrera S, Aguilera A. Molecular evidence for a positive role of Spt4 in transcription elongation. EMBO J. 2003;22:612-20 pubmed
    ..Our results indicate that Spt4-Spt5 has a positive role in transcription elongation and suggest that Spt4-Spt5 and THO act at different steps during mRNA biogenesis. ..
  4. González Barrera S, Prado F, Verhage R, Brouwer J, Aguilera A. Defective nucleotide excision repair in yeast hpr1 and tho2 mutants. Nucleic Acids Res. 2002;30:2193-201 pubmed
    ..We show that null mutations of the HPR1 and THO2 genes, encoding two prominent proteins of the THO complex, increase UV sensitivity of yeast cells lacking ..
  5. Gwizdek C, Iglesias N, Rodriguez M, Ossareh Nazari B, Hobeika M, Divita G, et al. Ubiquitin-associated domain of Mex67 synchronizes recruitment of the mRNA export machinery with transcription. Proc Natl Acad Sci U S A. 2006;103:16376-81 pubmed
    ..Our results reveal that the UBA domain of Mex67 directly interacts with polyubiquitin chains and with Hpr1, a component of the THO/TREX complex, which is regulated by ubiquitylation in a transcription-dependent manner...
  6. Gaillard H, Wellinger R, Aguilera A. A new connection of mRNP biogenesis and export with transcription-coupled repair. Nucleic Acids Res. 2007;35:3893-906 pubmed
    ..Our results indicate that RNAPII is not proficient for TCR in mRNP biogenesis and export mutants, opening new perspectives on our knowledge of TCR in eukaryotic cells. ..
  7. Aguilera A, Klein H. HPR1, a novel yeast gene that prevents intrachromosomal excision recombination, shows carboxy-terminal homology to the Saccharomyces cerevisiae TOP1 gene. Mol Cell Biol. 1990;10:1439-51 pubmed
    The HPR1 gene has been cloned by complementation of the hyperrecombination phenotype of hpr1-1 strains by using a color assay system...
  8. Zenklusen D, Vinciguerra P, Wyss J, Stutz F. Stable mRNP formation and export require cotranscriptional recruitment of the mRNA export factors Yra1p and Sub2p by Hpr1p. Mol Cell Biol. 2002;22:8241-53 pubmed
    ..We identified genetic and physical interactions between Yra1p, Sub2p, and Hpr1p, a protein involved in transcription elongation whose deletion leads to poly(A)(+) RNA accumulation in the nucleus...
  9. Gómez González B, Felipe Abrio I, Aguilera A. The S-phase checkpoint is required to respond to R-loops accumulated in THO mutants. Mol Cell Biol. 2009;29:5203-13 pubmed publisher
    ..In light of these results, we propose a model in which R-loop-mediated recombination is explained by template switching. ..

More Information

Publications64

  1. Chanarat S, Seizl M, Strasser K. The Prp19 complex is a novel transcription elongation factor required for TREX occupancy at transcribed genes. Genes Dev. 2011;25:1147-58 pubmed publisher
  2. Jimeno S, Rondón A, Luna R, Aguilera A. The yeast THO complex and mRNA export factors link RNA metabolism with transcription and genome instability. EMBO J. 2002;21:3526-35 pubmed
    The THO complex is a multimeric factor containing four polypeptides, Tho2, Hpr1, Mft1 and Thp2...
  3. Piruat J, Aguilera A. A novel yeast gene, THO2, is involved in RNA pol II transcription and provides new evidence for transcriptional elongation-associated recombination. EMBO J. 1998;17:4859-72 pubmed
    ..We propose that there is a set of proteins including Hpr1p and Tho2p, in the absence of which RNA pol II transcription is stalled or blocked, causing genetic instability.
  4. Röther S, Clausing E, Kieser A, Strasser K. Swt1, a novel yeast protein, functions in transcription. J Biol Chem. 2006;281:36518-25 pubmed
    ..Importantly, deletion of Swt1 leads to decreased transcription. Taken together, these data suggest that Swt1 functions in gene expression in conjunction with the TREX complex. ..
  5. Huertas P, Aguilera A. Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol Cell. 2003;12:711-21 pubmed
    ..These data support a model to explain the connection between recombination, transcription, and mRNA metabolism and provide a new perspective to understanding transcription-associated recombination. ..
  6. Chavez S, Beilharz T, Rondón A, Erdjument Bromage H, Tempst P, Svejstrup J, et al. A protein complex containing Tho2, Hpr1, Mft1 and a novel protein, Thp2, connects transcription elongation with mitotic recombination in Saccharomyces cerevisiae. EMBO J. 2000;19:5824-34 pubmed
    ..We have shown previously that the yeast genes HPR1 and THO2 may be keys to the understanding of transcription-associated recombination, as they both affect ..
  7. Garcia Rubio M, Chávez S, Huertas P, Tous C, Jimeno S, Luna R, et al. Different physiological relevance of yeast THO/TREX subunits in gene expression and genome integrity. Mol Genet Genomics. 2008;279:123-32 pubmed
    ..THO is composed of Tho2, Hpr1, Mft1 and Thp2 subunits, which associate with the Sub2-Yra1 export factors and Tex1 to form the TREX complex...
  8. Fan H, Merker R, Klein H. High-copy-number expression of Sub2p, a member of the RNA helicase superfamily, suppresses hpr1-mediated genomic instability. Mol Cell Biol. 2001;21:5459-70 pubmed
    We report on a novel role for a pre-mRNA splicing component in genome stability. The Hpr1 protein, a component of an RNA polymerase II complex and required for transcription elongation, is also required for genome stability...
  9. Gómez González B, Garcia Rubio M, Bermejo R, Gaillard H, Shirahige K, Marin A, et al. Genome-wide function of THO/TREX in active genes prevents R-loop-dependent replication obstacles. EMBO J. 2011;30:3106-19 pubmed publisher
    ..Chromatin immunoprecipitation (ChIP)-chip studies reveal that the Hpr1 component of THO and the Sub2 RNA-dependent ATPase have genome-wide distributions at active ORFs in yeast...
  10. Peña A, Gewartowski K, Mroczek S, Cuellar J, Szykowska A, Prokop A, et al. Architecture and nucleic acids recognition mechanism of the THO complex, an mRNP assembly factor. EMBO J. 2012;31:1605-16 pubmed publisher
    ..In yeast, this complex has been described as a heterotetramer (Tho2, Hpr1, Mft1, and Thp2) that interacts with Tex1 and mRNA export factors Sub2 and Yra1 to form the TRanscription EXport (..
  11. Strasser K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez Navarro S, et al. TREX is a conserved complex coupling transcription with messenger RNA export. Nature. 2002;417:304-8 pubmed
    ..We also show that Sub2 and Yra1 interact genetically with all four components of the THO complex (Tho2, Hpr1, Mft1 and Thp2)...
  12. Vinciguerra P, Iglesias N, Camblong J, Zenklusen D, Stutz F. Perinuclear Mlp proteins downregulate gene expression in response to a defect in mRNA export. EMBO J. 2005;24:813-23 pubmed
    ..Defects in Yra1p prevent mRNPs from crossing the Mlp gate and this block negatively feeds back on the transcription of a subset of genes, suggesting that Mlps link mRNA transcription and export. ..
  13. Hobeika M, Brockmann C, Gruessing F, Neuhaus D, Divita G, Stewart M, et al. Structural requirements for the ubiquitin-associated domain of the mRNA export factor Mex67 to bind its specific targets, the transcription elongation THO complex component Hpr1 and nucleoporin FXFG repeats. J Biol Chem. 2009;284:17575-83 pubmed publisher
    ..cerevisiae mRNA nuclear export factor, Mex67, can bind both nuclear pore protein (nucleoporin) FG repeats and Hpr1, a component of the TREX.THO complex that functions to link transcription and export...
  14. Piruat J, Chavez S, Aguilera A. The yeast HRS1 gene is involved in positive and negative regulation of transcription and shows genetic characteristics similar to SIN4 and GAL11. Genetics. 1997;147:1585-94 pubmed
    ..evidence that HRS1/PGD1, a yeast gene previously identified as a suppressor of the hyper-recombination phenotype of hpr1, has positive and negative roles in transcriptional regulation...
  15. Jensen T, Boulay J, Olesen J, Colin J, Weyler M, Libri D. Modulation of transcription affects mRNP quality. Mol Cell. 2004;16:235-44 pubmed
    ..Our results suggest that efficient mRNP assembly is under a kinetic control that is influenced by the rate of transcription. ..
  16. Jimeno S, Tous C, García Rubio M, Ranes M, González Aguilera C, Marin A, et al. New suppressors of THO mutations identify Thp3 (Ypr045c)-Csn12 as a protein complex involved in transcription elongation. Mol Cell Biol. 2011;31:674-85 pubmed publisher
    ..of this coupling, we have performed a search for suppressors of the transcription defect caused by the hpr1? mutation...
  17. Bermejo R, Capra T, Jossen R, Colosio A, Frattini C, Carotenuto W, et al. The replication checkpoint protects fork stability by releasing transcribed genes from nuclear pores. Cell. 2011;146:233-46 pubmed publisher
  18. Gwizdek C, Hobeika M, Kus B, Ossareh Nazari B, Dargemont C, Rodriguez M. The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation. J Biol Chem. 2005;280:13401-5 pubmed
    ..Here, we identified Hpr1p, a member of the THO/TREX (transcription/export) complex that couples mRNA transcription to nuclear export as a ..
  19. Katta S, Chen J, Gardner J, Friederichs J, Smith S, Gogol M, et al. Sec66-Dependent Regulation of Yeast Spindle-Pole Body Duplication Through Pom152. Genetics. 2015;201:1479-95 pubmed publisher
  20. Chang M, Bellaoui M, Boone C, Brown G. A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage. Proc Natl Acad Sci U S A. 2002;99:16934-9 pubmed
    ..These genes may promote replication fork stability or processivity during encounters between replication forks and DNA damage. ..
  21. Merker R, Klein H. Role of transcription in plasmid maintenance in the hpr1Delta mutant of Saccharomyces cerevisiae. Mol Cell Biol. 2002;22:8763-73 pubmed
    ..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 hpr1Delta mutant ..
  22. Yu T, Wang C, Lin J. Depleting components of the THO complex causes increased telomere length by reducing the expression of the telomere-associated protein Rif1p. PLoS ONE. 2012;7:e33498 pubmed publisher
    ..However, genome-wide analysis of Saccharomyces cerevisiae mutants has revealed that deletion of Hpr1p, a component of the THO complex, also affects telomere length...
  23. Piruat J, Aguilera A. Mutations in the yeast SRB2 general transcription factor suppress hpr1-induced recombination and show defects in DNA repair. Genetics. 1996;143:1533-42 pubmed
    ..and molecular evidence that the hrs2-1 mutation, isolated as a suppressor of the hyperrecombination phenotype of hpr1 delta, is in the SRB2 gene, which encodes a component of the RNA polII holoenzyme...
  24. Castellano Pozo M, Santos Pereira J, Rondon A, Barroso S, Andújar E, Pérez Alegre M, et al. R loops are linked to histone H3 S10 phosphorylation and chromatin condensation. Mol Cell. 2013;52:583-90 pubmed publisher
    ..Such histone modifications were also observed in R-loop-accumulating Caenorhabditis elegans and HeLa cells. We therefore provide a role of RNA in chromatin structure essential to understand how R loops modulate genome dynamics. ..
  25. Castellano Pozo M, Garcia Muse T, Aguilera A. R-loops cause replication impairment and genome instability during meiosis. EMBO Rep. 2012;13:923-9 pubmed publisher
    ..Importantly, RNase H partially suppressed the replication impairment and the DNA-damage accumulation. We conclude that R-loops can form during meiosis causing replication impairment with deleterious results. ..
  26. Lazzaro F, Novarina D, Amara F, Watt D, Stone J, Costanzo V, et al. RNase H and postreplication repair protect cells from ribonucleotides incorporated in DNA. Mol Cell. 2012;45:99-110 pubmed publisher
  27. Sadoff B, Heath Pagliuso S, Castaño I, Zhu Y, Kieff F, Christman M. Isolation of mutants of Saccharomyces cerevisiae requiring DNA topoisomerase I. Genetics. 1995;141:465-79 pubmed
    ..The TRF genes define at least four complementation groups. TRF3 is allelic to TOP2. TRF1 is allelic to HPR1, previously shown to be homologous to TOP1 over two short regions...
  28. Chang M, French Cornay D, Fan H, Klein H, Denis C, Jaehning J. A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling. Mol Cell Biol. 1999;19:1056-67 pubmed
    ..Shi et al., Mol. Cell. Biol. 17:1160-1169, 1997). In this work we demonstrate that Ccr4p and Hpr1p are components of the Paf1p-Cdc73p-Pol II complex...
  29. Meinel D, Burkert Kautzsch C, Kieser A, O Duibhir E, Siebert M, Mayer A, et al. Recruitment of TREX to the transcription machinery by its direct binding to the phospho-CTD of RNA polymerase II. PLoS Genet. 2013;9:e1003914 pubmed publisher
    ..In summary, we provide insight into how the phospho-code of the CTD directs mRNP formation and export through TREX recruitment...
  30. Ossareh Nazari B, Cohen M, Dargemont C. The Rsp5 ubiquitin ligase and the AAA-ATPase Cdc48 control the ubiquitin-mediated degradation of the COPII component Sec23. Exp Cell Res. 2010;316:3351-7 pubmed publisher
    ..Our data favor the idea that Cdc48 plays a key role in deciphering fates of ubiquitylated Sec23 to degradation or deubiquitylation/stabilization via its cofactors. ..
  31. Zhu Y, Peterson C, Christman M. HPR1 encodes a global positive regulator of transcription in Saccharomyces cerevisiae. Mol Cell Biol. 1995;15:1698-708 pubmed
    The Hpr1 protein has an unknown function, although it contains a region of homology to DNA topoisomerase I...
  32. Park H, Sternglanz R. Identification and characterization of the genes for two topoisomerase I-interacting proteins from Saccharomyces cerevisiae. Yeast. 1999;15:35-41 pubmed
    ..TOF2 shows various genetic interactions with TOP1 and HPR1. The implications of these interactions for TOF2 function are discussed.
  33. Libri D, Dower K, Boulay J, Thomsen R, Rosbash M, Jensen T. Interactions between mRNA export commitment, 3'-end quality control, and nuclear degradation. Mol Cell Biol. 2002;22:8254-66 pubmed
    ..overexpression of the mRNA export factor Sub2p suppresses the growth defect of hpr1 null cells, yet the protein Hpr1p and the associated THO protein complex are implicated in transcriptional elongation...
  34. Zhang Y, French S, Beyer A, Schneider D. The Transcription Factor THO Promotes Transcription Initiation and Elongation by RNA Polymerase I. J Biol Chem. 2016;291:3010-8 pubmed publisher
    ..Pol I transcription in hpr1 or tho2 null mutants is dramatically reduced to less than 20% of the WT level...
  35. Park H, Sternglanz R. Two separate conserved domains of eukaryotic DNA topoisomerase I bind to each other and reconstitute enzymatic activity. Chromosoma. 1998;107:211-5 pubmed
    ..Coexpression of these two domains in yeast partially complemented the growth defects of top1-top2ts and top1-hpr1 mutants...
  36. Merker R, Klein H. hpr1Delta affects ribosomal DNA recombination and cell life span in Saccharomyces cerevisiae. Mol Cell Biol. 2002;22:421-9 pubmed
    ..Here we show that loss of a component of the RNA polymerase II complex, Hpr1p, results in a decreased life span...
  37. Fan H, Klein H. Characterization of mutations that suppress the temperature-sensitive growth of the hpr1 delta mutant of Saccharomyces cerevisiae. Genetics. 1994;137:945-56 pubmed
    The hpr1 delta 3 mutant of Saccharomyces cerevisiae is temperature-sensitive for growth at 37 degrees and has a 1000-fold increase in deletion of tandem direct repeats...
  38. Martínez Lumbreras S, Taverniti V, Zorrilla S, Séraphin B, Pérez Cañadillas J. Gbp2 interacts with THO/TREX through a novel type of RRM domain. Nucleic Acids Res. 2016;44:437-48 pubmed publisher
    ..These findings provide structural and functional insights into the contribution of SR-like proteins in the post-transcriptional control of gene expression. ..
  39. Hobeika M, Brockmann C, Iglesias N, Gwizdek C, Neuhaus D, Stutz F, et al. Coordination of Hpr1 and ubiquitin binding by the UBA domain of the mRNA export factor Mex67. Mol Biol Cell. 2007;18:2561-8 pubmed
    ..elongation and nuclear export by interacting both with ubiquitin conjugates and specific targets, such as Hpr1, a component of the THO complex...
  40. Fan H, Cheng K, Klein H. Mutations in the RNA polymerase II transcription machinery suppress the hyperrecombination mutant hpr1 delta of Saccharomyces cerevisiae. Genetics. 1996;142:749-59 pubmed
    ..and soh4 mutants were isolated as suppressors of the temperature-dependent growth of the hyperrecombination mutant hpr1 of Saccharomyces cerevisiae...
  41. Santos Pereira J, Herrero A, García Rubio M, Marin A, Moreno S, Aguilera A. The Npl3 hnRNP prevents R-loop-mediated transcription-replication conflicts and genome instability. Genes Dev. 2013;27:2445-58 pubmed publisher
    ..Therefore, our work demonstrates that mRNP factors are critical for genome integrity and opens the option of using them as therapeutic targets in anti-cancer treatment. ..
  42. Pfeiffer V, Crittin J, Grolimund L, Lingner J. The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening. EMBO J. 2013;32:2861-71 pubmed publisher
    ..Altogether, our data indicate that THO, through the interplay with TERRA, regulates chromosome end processing activities and prevents interference with semiconservative DNA replication of telomeric DNA...
  43. Aguilera A, Klein H. Genetic control of intrachromosomal recombination in Saccharomyces cerevisiae. I. Isolation and genetic characterization of hyper-recombination mutations. Genetics. 1988;119:779-90 pubmed
    ..hpr4, hpr5 and hpr8) between repeated sequences, some increase loss of a marker between duplicated genes (hpr1 and hpr6), and some increase both types of events (hpr2, hpr3 and hpr7)...
  44. Skruzny M, Schneider C, Rácz A, Weng J, Tollervey D, Hurt E. An endoribonuclease functionally linked to perinuclear mRNP quality control associates with the nuclear pore complexes. PLoS Biol. 2009;7:e8 pubmed publisher
    ..The data suggest that Swt1 endoribonuclease might be transiently recruited to NPCs to initiate the degradation of defective pre-mRNPs or mRNPs trapped at nuclear periphery in order to avoid their cytoplasmic export and translation...
  45. Jimeno S, Luna R, Garcia Rubio M, Aguilera A. Tho1, a novel hnRNP, and Sub2 provide alternative pathways for mRNP biogenesis in yeast THO mutants. Mol Cell Biol. 2006;26:4387-98 pubmed
    ..Overexpression of Tho1 or Sub2 may provide alternative ways for mRNP formation and export in the absence of a functional THO complex. ..
  46. Herrera Moyano E, Mergui X, Garc a Rubio M, Barroso S, Aguilera A. The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts. Genes Dev. 2014;28:735-48 pubmed publisher
    ..The results demonstrate a key function of FACT in the resolution of R-loop-mediated transcription-replication conflicts, likely associated with a specific chromatin organization...
  47. Uemura H, Pandit S, Jigami Y, Sternglanz R. Mutations in GCR3, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, suppress the temperature-sensitive growth of hpr1 mutants. Genetics. 1996;142:1095-103 pubmed
    ..Plasmid DNA isolated from gcr3 mutants was significantly more negatively supercoiled than normal, suggesting that Gcr3 protein, like topoisomerase I and Hpr1p, affects chromatin structure, perhaps during transcription.
  48. García Rubio M, Aguilera A. Topological constraints impair RNA polymerase II transcription and causes instability of plasmid-borne convergent genes. Nucleic Acids Res. 2012;40:1050-64 pubmed publisher
    ..Our work shows that topological constraints negatively affect RNAPII transcription and genetic integrity, and provides an assay to study gene regulation by transcription interference. ..
  49. Bonnet A, Bretes H, Palancade B. Nuclear pore components affect distinct stages of intron-containing gene expression. Nucleic Acids Res. 2015;43:4249-61 pubmed publisher
    ..Our study thus highlights the multiplicity of mechanisms by which nuclear pores contribute to gene expression, and further provides the first evidence that intronic sequences can alleviate early mRNP biogenesis defects. ..
  50. Li B, Lustig A. A novel mechanism for telomere size control in Saccharomyces cerevisiae. Genes Dev. 1996;10:1310-26 pubmed
    ..The deletion of telomeres to wild-type lengths is stimulated by the hpr1 mutation, suggesting that TRD in these cells is the consequence of an intrachromatid pathway...
  51. Santos Rosa H, Aguilera A. Isolation and genetic analysis of extragenic suppressors of the hyper-deletion phenotype of the Saccharomyces cerevisiae hpr1 delta mutation. Genetics. 1995;139:57-66 pubmed
    The HPR1 gene of Saccharomyces cerevisiae is involved in maintaining low levels of deletions between DNA repeats...
  52. Jimeno S, Garcia Rubio M, Luna R, Aguilera A. A reduction in RNA polymerase II initiation rate suppresses hyper-recombination and transcription-elongation impairment of THO mutants. Mol Genet Genomics. 2008;280:327-36 pubmed publisher
    ..This study furthers the understanding of the importance of THO in transcription and the maintenance of genome stability. ..
  53. Mueller C, Jaehning J. Ctr9, Rtf1, and Leo1 are components of the Paf1/RNA polymerase II complex. Mol Cell Biol. 2002;22:1971-80 pubmed
    ..We suggest that lack of Paf1 results in a defective complex and a block in transcription, which is relieved by removal of Leo1 or Rtf1. ..
  54. Grund S, Fischer T, Cabal G, Antúnez O, Pérez Ortín J, Hurt E. The inner nuclear membrane protein Src1 associates with subtelomeric genes and alters their regulated gene expression. J Cell Biol. 2008;182:897-910 pubmed publisher
    ..Our data show that the inner nuclear membrane protein Src1 functions at the interface between subtelomeric gene expression and TREX-dependent messenger RNA export through the nuclear pore complexes. ..
  55. Preker P, Guthrie C. Autoregulation of the mRNA export factor Yra1p requires inefficient splicing of its pre-mRNA. RNA. 2006;12:994-1006 pubmed
    ..We propose that appropriate levels of Yra1p are maintained by inefficient cotranscriptional splicing. ..