How mycobacteria engage a transcription factor to respond to DNA damage
Following insults to their genome cells mount a stress response, allowing the organism to survive and repair otherwise lethal lesions. A new study by the Weber-Ban group investigates how mycobacteria engage transcription factor PafBC to respond to DNA damage. The findings help understand the biology of mycobacteria including the pathogenic species that causes tuberculosis.
Most bacteria react to DNA damage through the so-called SOS response. In mycobacteria, however, a second pathway regulates the majority of DNA repair genes. Recently, the heterodimeric complex PafBC was identified as the transcriptional activator of this LexA/RecA-independent pathway. PafBC belongs to a broadly distributed family of bacterial transcriptional regulators that are poorly understood due to a lack of structural information outside the predicted DNA-binding domains. The Weber-Ban group now determined the crystal structure of a PafBC complex revealing a structural similarity to protein domains frequently encountered in RNA-binding proteins. The domain arrangement in the PafBC structure shows that in order to bind target DNA a conformational rearrangement is required, which might be triggered by a co-activating RNA or other nucleic acid ligand accepted at the RNA-binding domains. In vivo complementation studies with PafBC carrying substitutions in putative RNA-binding motifs of these domains lend support to this model of transcriptional activation.
Link to the publication in external page Nature Communications