The Yeast Hrs1 Gene Is Involved in Positive and Negative Regulation of Transcription and Shows Genetic Characteristics Similar to Sin4 and Gal11

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We provide genetic 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. We have analyzed three differently regulated promoters, GAL1, PHO5 and HSP26, by β-galactosidase assays of lacZ-fused promoters and by Northern analysis of the endogenous genes. Transcription of these promoters was derepressed in hrs1δ mutants under conditions in which it is normally repressed in wild type. Under induced conditions it was either strongly reduced or significantly enhanced depending on the promoter system analyzed. Constitutive transcription was not affected, as determined in ADH1 and TEF2. In addition, Hrs1p was required for mating-factor expression, telomere-linked DNA silencing and DNA supercoiling of plasmids. Furthermore, hrs1δ suppressed Ty-insertion mutations and conferred a Gal(-) phenotype. Many of these phenotypes also result from mutations in GAL11, SIN4 or RGR1, which encode proteins of the RNA polII mediator. We also show that gal11δ and sin4δ partially suppress the hyper-rec phenotype of hpr1 mutants, although to a lesser extent than hrs1δ. Our results provide new evidence for the connection between hpr1δ-induced deletions and transcription. We discuss the possibility that Hrs1p might be a component of the RNA polII transcription machinery.

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