Regulation of ribosomal DNA stability by gas1 mutant and rho0 mutant in Saccharomyces cerevisiae.

Abstract

In budding yeast, rDNA has a tandem repeat array of 9.1 kbp each rDNA unit by 100~200 copies. rDNA silencing process controls the stability of this highly repetitive region. Here, we report that Gas1 controls transcriptional silencing of rDNA by PKA signaling pathway. Gas1 is β-1,3-glucanosyltransferase and has a role in cell wall organization. Deletion of Gas1 decreases PKA activity, it causes dephosphorylation of two stress response transcription factors, Msn2 and Msn4. Dephosphorylated form of Msn2/4 can get into nucleus from the cytoplasm and promote the transcription of Pnc1, the activator of Sir2 which forms RENT complexes and silences rDNA. Moreover, cell wall damage reagent Congo red treated cell also shows similar pattern of increased Sir2-mediated rDNA silencing. Unlike in gas1Δmutant, PKA activity is induced in rho0mutant which is mitochondrial respiratory malfunction by mtDNA loss. Increased activity of PKA in rho0 mutant leads to decreased rDNA silencing. These findings suggest that gas1Δ mutant and rho0 mutant influence rDNA stability by controlling PKA pathway.