Suppression analysis of esa1 mutants in Saccharomyces cerevisiae links NAB3 to transcriptional silencing and nucleolar functions.
The acetyltransferase Esa1 is essential in the yeast Saccharomyces cerevisiae and plays a critical role in multiple cellular processes. The most well-defined targets for Esa1 are lysine residues on histones. However, an increasing number of nonhistone proteins have recently been identified as substrates of Esa1. In this study, four genes (LYS20, LEU2, VAP1, and NAB3) were identified in a genetic screen as high-copy suppressors of the conditional temperature-sensitive lethality of an esa1 mutant. When expressed from a high-copy plasmid, each of these suppressors rescued the temperature-sensitivity of an esa1 mutant. Only NAB3 overexpression also rescued the rDNA-silencing defects of an esa1 mutant. Strengthening the connections between NAB3 and ESA1, mutants of nab3 displayed several phenotypes similar to those of esa1 mutants, including increased sensitivity to the topoisomerase I inhibitor camptothecin and defects in rDNA silencing and cell-cycle progression. In addition, nuclear localization of Nab3 was altered in the esa1 mutant. Finally, posttranslational acetylation of Nab3 was detected in vivo and found to be influenced by ESA1.
Division of Biological Sciences and Moores Cancer Center, University of California-San Diego, La Jolla, California 92093-0347, USA.
Christie S
CS
Chang
Astrid
A
Clarke
Lorraine
L
Pillus
D000107:Acetylation; D002466:Cell Nucleolus / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013489:Suppression, Genetic; D014158:Transcription, Genetic
D006657:Histones; C090564:NAB3 protein, S cerevisiae; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C496551:Esa1 protein, S cerevisiae; D051548:Histone Acetyltransferases