The PafBC-mediated response sensitizes a bistable DNA damage response in Mycobacteria

Cody E FitzGerald; James P Keener

doi:10.1016/j.jtbi.2020.110462

The PafBC-mediated response sensitizes a bistable DNA damage response in Mycobacteria

J Theor Biol. 2021 Jan 7:508:110462. doi: 10.1016/j.jtbi.2020.110462. Epub 2020 Sep 2.

Authors

Cody E FitzGerald¹, James P Keener²

Affiliations

¹ University of Utah, Department of Mathematics, 155 South 1400 East, Salt Lake City, UT 84112, United States. Electronic address: cfitz@math.utah.edu.
² University of Utah, Department of Mathematics, 155 South 1400 East, Salt Lake City, UT 84112, United States.

PMID: 32890555
DOI: 10.1016/j.jtbi.2020.110462

Abstract

Due to the genotoxically challenging environments in which they live in, Mycobacteria have a complex DNA damage repair system that is governed by two major DNA damage responses, namely, the LexA/RecA-dependent response and the newly characterized PafBC-mediated response (Müller et al., 2018). The LexA/RecA-dependent response is a well-known bistable response found in different types of bacteria, and the Mycobacteria-specific PafBC-mediated response interacts with and modifies the LexA/RecA-dependent response (Müller et al., 2018). The interaction between the LexA/RecA-dependent response and the PafBC-mediated response has not been characterized mathematically. Our analysis shows that the addition of the PafBC-mediated response sensitizes the overall DNA damage response, effectively lowering the DNA damage rate threshold for activation.

Keywords: Bifurcation; DNA damage response model; Hystersis; LexA/RecA dependent response; PafBC-mediated response; SOS response; Switch-like.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Bacterial Proteins / genetics
DNA Damage
Mycobacterium*
SOS Response, Genetics*
Serine Endopeptidases

Substances

Bacterial Proteins
Serine Endopeptidases