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HPR1  -  Hpr1p

Saccharomyces cerevisiae S288c

Synonyms: Hyperrecombination protein 1, THO complex subunit HPR1, YD9302.14, YDR138W
 
 
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High impact information on HPR1

  • The yeast HPR1 gene has a functional role in transcriptional elongation that uncovers a novel source of genome instability [1].
  • We show that HPR1 is not required for transcription activation and that the previously reported effects of hpr1Delta on the activation of different promoters is a consequence of the incapacity of hpr1Delta cells to elongate transcription through lacZ, used as reporter [1].
  • Defects in the chromatin-organizing protein Sir3p increase the rate of hpr1-induced rapid deletion and specifically change the spectrum of rapid deletion events [2].
  • 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 [2].
  • A modified chromatin immunoprecipitation assay that includes an RNase step indicates that Sub2p is bound to nascent RNA, Yra1p is associated with both RNA and DNA, and Hpr1p is associated with DNA [3].
 

Biological context of HPR1

  • The HPR1 gene has been cloned by complementation of the hyperrecombination phenotype of hpr1-1 strains by using a color assay system [4].
  • Deletion of HPR1 results in a 1,000-fold increase in genome instability, detected as direct-repeat instability [5].
  • HPR1 is a gene that is in single copy on chromosome IV of Saccharomyces cerevisiae, closely linked to ARO1, and it codes for a putative protein of 752 amino acids (molecular mass, 88 kilodaltons) [4].
  • The genomic instability observed in sub2 mutants can be suppressed by high-copy-number HPR1 [5].
  • Haploid strains carrying deletions of the HPR1 gene show a slightly reduced mitotic growth rate and extremely high rates of intrachromosomal excision recombination (frequency, 10 to 15%) but have a undetectable effect on rDNA recombination [4].
 

Anatomical context of HPR1

 

Associations of HPR1 with chemical compounds

  • The yeast HRS1 gene encodes a polyglutamine-rich nuclear protein required for spontaneous and hpr1-induced deletions between direct repeats [6].
  • On the other hand, the hrs2-1 mutation (renamed srb2-101), in which Gly150 has been changed to Asp, makes cells sensitive to long MMS treatments, a phenotype observed for the srb2 delta null allele only in a hpr1 delta background [8].
 

Regulatory relationships of HPR1

  • Further analysis showed that gcr3 mutations also suppressed the temperature-sensitive growth of hpr1 single mutants [9].
  • The transcriptional defect at HO and the CCB::lacZ upstream activation sequence in hpr1 mutants is partially suppressed by a deletion of SIN1, which encodes an HMG1p-like protein [10].
  • The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation [11].
  • Mutations in the yeast SRB2 general transcription factor suppress hpr1-induced recombination and show defects in DNA repair [8].
  • The simplest hypothesis to account for some of the hpr1 stimulated recombination events is that a heteroduplex DNA intermediate and localized gene conversion are involved. hpr1 stimulated crossover events are independent of intrachromosomal gene conversion events stimulated by the hyper-gene conversion mutation hpr5 [12].
 

Other interactions of HPR1

  • HPR1, a novel yeast gene that prevents intrachromosomal excision recombination, shows carboxy-terminal homology to the Saccharomyces cerevisiae TOP1 gene [4].
  • Mutations in GCR3, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, suppress the temperature-sensitive growth of hpr1 mutants [9].
  • Our work not only identifies a novel yeast gene, THO2, with similar function to HPR1, but also provides new evidence for transcriptional blocks as a source of recombination [13].
  • High-copy-number expression of Sub2p, a member of the RNA helicase superfamily, suppresses hpr1-mediated genomic instability [5].
  • Stable mRNP formation and export require cotranscriptional recruitment of the mRNA export factors Yra1p and Sub2p by Hpr1p [14].

References

  1. The yeast HPR1 gene has a functional role in transcriptional elongation that uncovers a novel source of genome instability. Chávez, S., Aguilera, A. Genes Dev. (1997) [Pubmed]
  2. A novel mechanism for telomere size control in Saccharomyces cerevisiae. Li, B., Lustig, A.J. Genes Dev. (1996) [Pubmed]
  3. Biochemical analysis of TREX complex recruitment to intronless and intron-containing yeast genes. Abruzzi, K.C., Lacadie, S., Rosbash, M. EMBO J. (2004) [Pubmed]
  4. HPR1, a novel yeast gene that prevents intrachromosomal excision recombination, shows carboxy-terminal homology to the Saccharomyces cerevisiae TOP1 gene. Aguilera, A., Klein, H.L. Mol. Cell. Biol. (1990) [Pubmed]
  5. High-copy-number expression of Sub2p, a member of the RNA helicase superfamily, suppresses hpr1-mediated genomic instability. Fan, H.Y., Merker, R.J., Klein, H.L. Mol. Cell. Biol. (2001) [Pubmed]
  6. The yeast HRS1 gene encodes a polyglutamine-rich nuclear protein required for spontaneous and hpr1-induced deletions between direct repeats. Santos-Rosa, H., Clever, B., Heyer, W.D., Aguilera, A. Genetics (1996) [Pubmed]
  7. Interactions between mRNA export commitment, 3'-end quality control, and nuclear degradation. Libri, D., Dower, K., Boulay, J., Thomsen, R., Rosbash, M., Jensen, T.H. Mol. Cell. Biol. (2002) [Pubmed]
  8. Mutations in the yeast SRB2 general transcription factor suppress hpr1-induced recombination and show defects in DNA repair. Piruat, J.I., Aguilera, A. Genetics (1996) [Pubmed]
  9. Mutations in GCR3, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, suppress the temperature-sensitive growth of hpr1 mutants. Uemura, H., Pandit, S., Jigami, Y., Sternglanz, R. Genetics (1996) [Pubmed]
  10. HPR1 encodes a global positive regulator of transcription in Saccharomyces cerevisiae. Zhu, Y., Peterson, C.L., Christman, M.F. Mol. Cell. Biol. (1995) [Pubmed]
  11. The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation. Gwizdek, C., Hobeika, M., Kus, B., Ossareh-Nazari, B., Dargemont, C., Rodriguez, M.S. J. Biol. Chem. (2005) [Pubmed]
  12. Genetic and molecular analysis of recombination events in Saccharomyces cerevisiae occurring in the presence of the hyper-recombination mutation hpr1. Aguilera, A., Klein, H.L. Genetics (1989) [Pubmed]
  13. A novel yeast gene, THO2, is involved in RNA pol II transcription and provides new evidence for transcriptional elongation-associated recombination. Piruat, J.I., Aguilera, A. EMBO J. (1998) [Pubmed]
  14. Stable mRNP formation and export require cotranscriptional recruitment of the mRNA export factors Yra1p and Sub2p by Hpr1p. Zenklusen, D., Vinciguerra, P., Wyss, J.C., Stutz, F. Mol. Cell. Biol. (2002) [Pubmed]
 
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