Yeast RNA polymerase I Core Factor binds to the ribosomal DNA promoter through the GC minor groove

Abstract

In Saccharomyces cerevisiae, Core Factor (CF) is a key evolutionary conserved transcription initiation factor that helps recruit RNA polymerase I (Pol I) to the ribosomal DNA (rDNA) promoter. Upregulated Pol I transcription has been linked to many cancers, and targeting Pol I is an attractive and emerging anti‐cancer strategy. Using the yeast model system, we characterized how CF binds to the Pol I promoter by electrophoretic mobility shift assays (EMSA). Synthetic DNA competitors along with anti‐tumor drugs and nucleic acid stains that act as DNA groove blockers were used to discover structural characteristics of CF binding. Our results show that CF employs a unique mechanism where it prefers the GC‐rich minor groove of the rDNA promoter, which may offer a new avenue to more specifically target upregulated Pol I activity in cancer.Support or Funding InformationThe work was supported by B.A.K. grants from the US National Institutes of Health (NIH) NCI (5K22CA184235), a Sinsheimer Scholar award from the Alexandrine and Alexander L. Sinsheimer Fund, Central New York Community Foundation, Joseph C. George Fund, and Virginia Simons & Dr. C. Adele Brown Fund.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.