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Cell Rep. 2018 Jun 19;23(12):3551-3564. doi: 10.1016/j.celrep.2018.05.073.

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

Author information

1
ETH Zurich, Institute of Molecular Biology and Biophysics, 8093 Zurich, Switzerland.
2
University of Zurich, Institute of Medical Microbiology, 8006 Zurich, Switzerland.
3
ETH Zurich, Institute of Molecular Biology and Biophysics, 8093 Zurich, Switzerland. Electronic address: eilika@mol.biol.ethz.ch.

Abstract

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.

KEYWORDS:

Clp gene regulator ClgR; DNA damage response; LexA/RecA-independent pathway; Mycobacterium smegmatis; PafBC regulon; RecA-NDp promoter; bacterial proteasome; pupylation

PMID:
29924998
DOI:
10.1016/j.celrep.2018.05.073
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