The Mycobacterial LexA/RecA-Independent DNA Damage Response Is Controlled by PafBC and the Pup-Proteasome System

Publication date: 19 June 2018
Source:Cell Reports, Volume 23, Issue 12
Author(s): Andreas U. Müller, Frank Imkamp, Eilika Weber-Ban
Mycobacteria exhibit two DNA damage response pathways: the LexA/RecA-dependent SOS response and a LexA/RecA-independent pathway. Using a combination of transcriptomics and genome-wide binding site analysis, we demonstrate that PafBC (proteasome accessory factor B and C), encoded in the Pup-proteasome system (PPS) gene locus, is the transcriptional regulator of the predominant LexA/RecA-independent pathway. Comparison of the resulting PafBC regulon with the DNA damage response of Mycobacterium smegmatis reveals that the majority of induced DNA repair genes are upregulated by PafBC. We further demonstrate that RecA, a member of the PafBC regulon and principal regulator of the SOS response, is degraded by the PPS when DNA damage stress has been overcome. Our results suggest a model for the regulation of the mycobacterial DNA damage response that employs the concerted action of PafBC as master transcriptional activator and the PPS for removal of DNA repair proteins to maintain a temporally controlled stress response.

Graphical abstract

Teaser

Müller et al. demonstrate that the Pup-proteasome gene locus harbors a transcriptional activator, PafBC, acting as the principal regulator of the mycobacterial DNA damage response, upregulating the majority of DNA repair genes. During stress recovery, the Pup-proteasome system removes DNA repair proteins to return the cell to its normal state.


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