DNA binding proteins are essential for cellular life, but persistently bound complexes have toxic consequences. Here we show that the proteotoxic responsive bacterial protease Lon clears proteins from DNA to promote genotoxic stress resistance. Purified Lon binds DNA and degrades neighboring bound proteins, while a fully active DNA-blind Lon variant does not. This variant can degrade substrates as normal during unstressed growth, complements pleotropic phenotypes of Δlon, including proteotoxic resilience, but remains sensitive to genotoxic stresses and fails to degrade proteins efficiently during DNA damage. Transposon sequencing reveals that Δlon is vulnerable to loss of protein-DNA eviction factors and we use dynamic nucleoid occupancy profiling to show that chromosome-wide protein turnover relies on Lon DNA binding. Finally, disrupting Lon binding to mitochondria genomes also results in genotoxic stress sensitivity, consistent with the bacterial ancestry of this organelle. We propose that clearance of persistent proteins from DNA by Lon originated in free-living α-proteobacteria and maintained during the evolution of mitochondria.
DNA binding by the Lon protease protects against genotoxic damage in a manner preserved from bacteria to mitochondria.
TI - A legacy role for DNA binding of Lon protects against genotoxic stress JO - bioRxiv DO - 10.1101/317677 DA - 2022-12-27 UR - https://www.deepdyve.com/lp/biorxiv/a-legacy-role-for-dna-binding-of-lon-protects-against-genotoxic-stress-NSXH5XbLE5 SP - 317677 DP - DeepDyve ER -