Promotion of hyperthermic-induced rDNA hypercondensation in Saccharomyces cerevisiae

Abstract

Ribosome biogenesis is tightly regulated through stress-sensing pathways that impact genome stability, aging and senescence. In Saccharomyces cerevisiae, ribosomal RNAs are transcribed from rDNA located on the right arm of chromosome XII. Numerous studies reveal that rDNA decondenses into a puff-like structure during interphase and condenses into a tight loop-like structure during mitosis. Intriguingly, a novel and additional mechanism of increased mitotic rDNA compaction (termed hypercondensation) was recently discovered that occurs in response to temperature stress (hyperthermic-induced) and is rapidly reversible. Here, we report that neither changes in condensin nor cohesin binding dynamics appear to play a critical role in hyperthermic-induced rDNA hypercondensation - differentiating this architectural state from normal mitotic condensation (requiring cohesins and condensins) and the premature condensation (requiring condensins) that occurs during interphase in response to nutrient starvation. A candidate genetic approach revealed that deletion of either Hsp82 or Hsc82 (Hsp90 heat shock paralogs) result in significantly reduced hyperthermic-induced rDNA hypercondensation. Intriguingly, Hsp inhibitors do not impact rDNA hypercondensation. In combination, these findings suggest that Hsp90 either stabilizes client proteins, which are sensitive to very transient thermic challenges, or directly promotes rDNA hypercondensation during preanaphase. Our findings further reveal that the high mobility group protein Hmo1 is a negative regulator of mitotic rDNA condensation, distinct from its role in promoting premature-condensation of rDNA during interphase upon nutrient starvation.