Superoxide dismutase 1 (Sod1) has been known for nearly half a century for catalysis of superoxide to hydrogen peroxide. Here we report a new Sod1 function in oxidative signalling: in response to elevated endogenous and exogenous reactive oxygen species (ROS), Sod1 rapidly relocates into the nucleus, which is important for maintaining genomic stability. Interestingly, H₂O₂ is sufficient to promote Sod1 nuclear localization, indicating that it is responding to general ROS rather than Sod1 substrate superoxide. ROS signalling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to promoters and regulates the expression of oxidative resistance and repair genes. Altogether, our study unravels an unorthodox function of Sod1 as a transcription factor and elucidates the regulatory mechanism for its localization.

The target of rapamycin (TOR) protein is a conserved regulator of ribosome biogenesis, an important process for cell growth and proliferation. However, how TOR is involved remains poorly understood. In this study, we find that rapamycin and nutrient starvation, conditions inhibiting TOR, lead to significant nucleolar size reduction in both yeast and mammalian cells. In yeast, this morphological change is accompanied by release of RNA polymerase I (Pol I) from the nucleolus and inhibition of ribosomal DNA (rDNA) transcription. We also present evidence that TOR regulates association of Rpd3–Sin3 histone deacetylase (HDAC) with rDNA chromatin, leading to site‐specific deacetylation of histone H4. Moreover, histone H4 hypoacetylation mutations cause nucleolar size reduction and Pol I delocalization, while rpd3 Ü and histone H4 hyperacetylation mutations block the nucleolar changes as a result of TOR inhibition. Taken together, our results suggest a chromatin‐mediated mechanism by which TOR modulates nucleolar structure, RNA Pol I localization and rRNA gene expression in response to nutrient availability.

Target of rapamycin (TOR) is a conserved regulator of gene expression from yeast to humans. In budding yeast, TOR is associated with ribosomal DNA (rDNA) promoter, which is critical for ribosome biogenesis and transfer RNA (tRNA) synthesis. Whether mTOR behaves similarly in mammalian cells is unknown. Here, we report that mTOR is detected at several different promoters in human and murine cells, including that of rDNA and tRNA genes. The association of mTOR with these promoters is regulated by growth signals and sensitive to rapamycin. Together, our observations suggest that mTOR is closely involved in gene regulation at the promoters, which is a conserved mechanism to control RNA polymerase I- and III-dependent genes that are critical for protein synthesis and cell growth.