High impact information on PPR1

• PPR1, a yeast activator with a similar zinc finger sequence, also responds to GAL11 and to GAL11P, whereas regulators bearing unrelated DNA binding motifs do not [1].
• By contrast, our results demonstrate that all but one of the 28 amino acids encompassing the single zinc-finger region of GAL4, the yeast transcriptional activator, can be replaced with the analogous zinc-finger region from another yeast-activator protein, PPR1, without changing the DNA-binding specificity of GAL4 [2].
• Moreover, substitution of the HAP1 dimerization domain with that of PPR1, which forms coiled-coils and dimerizes symmetrically, did not diminish the ability of the protein to bind selectively to a direct repeat [3].
• In comparison, a nontelomeric URA3 could be activated by PPR1 at all times [4].
• Whereas the GAL4 site has 11 intervening base pairs, the PPR1 site has 6 [5].

Biological context of PPR1

• The promoters of the unlinked but coordinately regulated URA1 and URA4 genes contain highly conserved copies of the UASURA sequence, which prompted us to investigate the effects of many point mutations within this UASURA sequence on PPR1-dependent binding [6].
• MEU1 is linked to PPR1 on chromosome XII [7].
• The DNA sequence of a 399-bp AccI-Bg/II fragment including 180 nucleotides of the 5'-flanking region of the gene PPR1 has been determined [8].
• Three in vitro-constructed deletions of PPR1 have been integrated at the chromosomal locus, giving strains with a completely negative phenotype [9].
• The ability of PPR1 to overcome silencing varied at different points in the cell cycle [4].

Associations of PPR1 with chemical compounds

• Expression of the yeast pyrimidine biosynthetic gene, URA3, is induced three- to fivefold in response to uracil starvation, and this regulation is mediated by the transcriptional activator PPR1 (pyrimidine pathway regulator 1) [6].
• A 16-base-pair sequence with dyad symmetry acts acts as a uracil-controlled upstream activating site (UASURA) and shows a specific binding only with cell extracts from strains overproducing PPR1 [6].
• In addition, we showed that UASURA contains a constitutive activating element which can stimulate transcription from a heterologous promoter independently of dihydroorotic acid and PPR1 [6].
• We have demonstrated that the six cysteine residues of the peptide chelate two cadmium ions as in GAL4 and PPR1 [10].
• The sequence and binding specificity of UaY, the specific regulator of the purine utilization pathway in Aspergillus nidulans, suggest an evolutionary relationship with the PPR1 protein of Saccharomyces cerevisiae [11].

Physical interactions of PPR1

• We have mapped an Upf1p-dependent destabilizing element to a region located within the 5'-UTR and the first 92 bases of the PPR1 ORF [12].

Regulatory relationships of PPR1

• Transcription of the two unlinked structural genes URA1 and URA3 of Saccharomyces cerevisiae is positively regulated by the gene product PPR1 [13].
• The PPR1 gene of Saccharomyces cerevisiae controls the transcription of two unlinked structural genes URA1 and URA3 [14].

Other interactions of PPR1

• Structures of two such domains, those from GAL4 and PPR1, have been solved as complexes with DNA [10].
• A regulatory gene PPR2 (pyrimidine pathway regulatory 2) acting specifically on this step, has been characterized, cloned and sequenced [15].
• To determine which portion of the LAC9 DNA-binding domain mediates sequence recognition, we replaced the C6 zinc finger, amino acids adjacent to the carboxyl side of the zinc finger, or both with the analogous region from the Saccharomyces cerevisiae PPR1 or LEU3 protein [16].
• A sequence similar to the motif surrounding serine 222 may play similar roles in the PPR1 and ADR1 proteins of Saccharomyces cerevisiae [17].
• Here we show that PPR1 mRNA degradation depends on the Upf proteins, Dcp1p, Xrn1p and Hrp1p [12].

Analytical, diagnostic and therapeutic context of PPR1

• The structures of the DNA binding domain-DNA complexes of two other zinc-cluster proteins (GAL4 and PPR1) have been studied by X-ray crystallography [18].

References