Single-stranded DNA binding to the transcription factor PafBC triggers the mycobacterial DNA damage response.

ABSTRACT: The DNA damage response in mycobacteria is controlled by the heterodimeric transcription factor PafBC, a member of the WYL domain-containing protein family. It has been shown that PafBC induces transcription of its regulon by reprogramming the housekeeping RNA polymerase holoenzyme to recognize PafBC-dependent promoters through sigma adaptation. However, the mechanism by which DNA damage is sensed and translated into PafBC activation has remained unclear. Here, we demonstrate that the binding of single-stranded DNA (ssDNA) to the WYL domains of PafBC activates the transcription factor. Our cryo-electron microscopy structure of full-length PafBC in its active conformation, bound to the transcription initiation complex, reveals a previously unknown mode of interaction between the ssDNA and t

SUBMITTER: Schilling CM 

PROVIDER: S-EPMC11804915 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature