A legacy role for DNA binding of Lon protects against genotoxic stress

Abstract

AbstractThe quality control protease Lon was originally characterized as a DNA binding protein, yet the physiological consequences of this interaction are not understood. Here we use the α-proteobacteriaCaulobacter crescentusto show that DNA binding of Lon is critical for DNA damage tolerance.In vitro, DNA can directly activate or inhibit Lon activity and promotes degradation of DNA bound proteins by neighboring bound Lon. Bacteria expressing a DNA-binding deficient Lon variant are phenotypically wildtype with respect to normal growth and response to proteotoxic stresses, but are sensitive to genotoxic stresses. Disrupting Lon binding to mitochondria genomes also results in sensitivity to DNA damage but otherwise maintained normal mitochondrial function, consistent with the bacterial ancestry of this organelle. We propose that clearance of overly persistent proteins from DNA, including DNA-protein crosslinks, by the Lon protease is an important damage response that originated in free-living α-proteobacteria and has been preserved during the endosymbiotic transition to mitochondria.One Sentence SummaryDNA binding by the Lon protease protects against genotoxic damage in a manner that has been preserved from bacteria to mitochondria.