Transcriptional management of mycobacterial DNA injury response by sigma adaptation

A latest research by the Weber-Ban and Ban teams (IMBB) revealed in Science Advances uncovers that the grasp regulator of the DNA injury response in mycobacteria, PafBC, leverages a novel mechanism of transcriptional activation to permit promoter recognition at promoters missing the canonical -35 motif.

At the transcriptional degree, mycobacteria, such because the human pathogen M. tuberculosis, reply to DNA injury by way of two intertwined regulatory pathways. One pathway constitutes the canonical SOS response, which is regulated by RecA and repressor LexA. The different, lately found pathway beneath management of regulator PafBC controls a lot of genes by transcription activation, together with recA. While the derepression mechanism of the SOS response is properly understood, PafBC’s mechanism of transcription activation remained unknown.

Researchers at IMBB found a novel mechanism of promoter recognition employed by PafBC. In micro organism, promoter recognition often entails two canonical sequence motifs positioned at positions -35 and -10 from the transcription begin web site. However, PafBC-dependent promoters will be thought-about “hybrid,” since they embody the canonical -10 area however lack the -35 motif and as an alternative function a PafBC-specific sequence motif at place -26. Using cryo-electron microscopy and biochemical experiments, the researchers visualized a PafBC-containing transcription initiation complicated. They present that PafBC features as an adaptor by inserting between the sigma subunit and the DNA in order that the RNA polymerase holoenzyme acknowledges a hybrid -26/-10 promoter, therefore this mechanism is known as “sigma adaptation.”

Genome-wide research discovered that many promoters in mycobacteria lack a canonical -35 motif. The mechanism of PafBC-dependent “sigma adaptation” may subsequently signify an instance of a widespread, various mode of bacterial promoter recognition employed additionally by different transcription elements.