Role of CURI complex in regulation of mTORC1 target genes under DNA damage stress Sanjay Kumar, Muneera Mashkoor, Priya Balamurugan, Anne Grove Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 mTORC1 (mechanistic target of rapamycin complex 1) promotes cell growth under conditions of amino acid sufficiency. In yeast, apart from nutrient starvation, DNA double strand breaks (DSBs) and nucleotide depletion also lead to mTORC1 inhibition. The yeast high mobility group protein Hmo1p binds along with other factors to ribosomal protein genes, RNA pol I-transcribed genes and to its own promoter. Expression of HMO1 is suppressed in response to DSB and nucleotide depletion and by mTORC1 inhibition by rapamycin. One of the Hmo1p partner proteins is Ifhl1p. Inhibition of mTORC1 causes the dissociation of Ifhl1p from the HMO1 and ribosomal protein gene promoters, followed by its movement to the nucleolus where it forms a complex with CK2p, Utp22p and Rrp7p, a complex named CURI. This complex formation synergistically functions in decreasing ribosomal biogenesis by sequestering Utp22p and Rrp7p, which are needed for pre-rRNA processing. We report here that DNA DSB induction or rapamycin treatment decreases the relative mRNA abundance of UTP22 and RRP7 up to five-fold. We also show that both Ifh1p and Hmo1p bind the UTP22 and RRP7 gene promoters during balanced growth, and that they dissociate upon DSB formation or rapamycin treatment, conditions under which the corepressor Crf1p is recruited. While reduced HMO1 mRNA levels in response to rapamycin requires direct binding of Tor1p at the HMO1 promoter, deletion of TOR1 did not markedly affect the expression of UTP22 or RRP7 upon rapamycin treatment. Consistent with this observation, preliminary data suggests the absence Tor1p at UTP22 and RRP7 promoters. We therefore propose that Tor2p can substitute for Tor1p in mTORC1 for the purpose of regulation of UTP22 and RRP7 expression. Notably, the reduced UTP22 and RRP7 mRNA levels observed under DNA damage stress or nutrient limitation (as mimicked by rapamycin treatment) would contribute to the reduction in ribosome biogenesis required for energy conservation under such conditions.