Coexistence of SOS-Dependent and SOS-Independent Regulation of DNA Repair Genes in Radiation-Resistant Deinococcus Bacteria

Abstract

Deinococcus bacteria are extremely resistant to radiation and able to repair a shattered genome in an essentially error-free manner after exposure to high doses of radiation or prolonged desiccation. An efficient, SOS-independent response mechanism to induce various DNA repair genes such as recA is essential for radiation resistance. This pathway, called radiation/desiccation response, is controlled by metallopeptidase IrrE and repressor DdrO that are highly conserved in Deinococcus. Among various Deinococcus species, Deinococcus radiodurans has been studied most extensively. Its genome encodes classical DNA repair proteins for error-free repair but no error-prone translesion DNA polymerases, which may suggest that absence of mutagenic lesion bypass is crucial for error-free repair of massive DNA damage. However, many other radiation-resistant Deinococcus species do possess translesion polymerases, and radiation-induced mutagenesis has been demonstrated. At least dozens of Deinococcus species contain a mutagenesis cassette, and some even two cassettes, encoding error-prone translesion polymerase DnaE2 and two other proteins, ImuY and ImuB-C, that are probable accessory factors required for DnaE2 activity. Expression of this mutagenesis cassette is under control of the SOS regulators RecA and LexA. In this paper, we review both the RecA/LexA-controlled mutagenesis and the IrrE/DdrO-controlled radiation/desiccation response in Deinococcus.

Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace

“…The SOS response is referred to as an inducible DNA repair process in response to DNA injury and oxidative stress. 51 , 52 The SOS pathway is important in bacterial adaptation, pathogenesis, and diversification, and thus, also important in the development of persister cells, extended tolerance, and stress resistance (including antibiotic resistance) (Figure 2 ). 53 According to a study conducted by Kohanski et al, it was reported that antibiotic exposure triggered the SOS response, and bacterial mutants that are unable to form iron–sulfur clusters became less susceptible to bactericidal antibiotics.…”

“…The RecA protein has also been generally identified as the first actor in initiating the SOS response by binding to single‐stranded DNA. 51 , 53 This emerging evidence linking antibiotic action and, as a result, cellular response to hydroxyl radical‐induced macromolecular damage can now be leveraged to develop new antibacterial agents. Inhibitors of the SOS response can not only prevent the development of antibiotic resistance, particularly, when the drug is present in sub‐lethal concentrations, but they can also enhance the activities of bactericidal antibiotics.…”

“…The SOS response triggers a higher rate of mutation, resulting in genetic diversification and microbial adaptation, including antibiotic persistence and resistance. 51 , 53 This method could be applied to any other critical proteins involved in the hydroxyl radical response. They may have been ignored in past efforts to uncover new antibiotic targets since they are not essential for cell growth.…”

“…However, it has been observed to play a much broader role. The SOS response triggers a higher rate of mutation, resulting in genetic diversification and microbial adaptation, including antibiotic persistence and resistance 51,53 . This method could be applied to any other critical proteins involved in the hydroxyl radical response.…”

Characterization of the Radiation Desiccation Response Regulon of the Radioresistant Bacterium Deinococcus radiodurans by Integrative Genomic Analyses

“…The IrrE/DdrO protein pair is highly conserved in Deinococcus species, and genes encoding IrrE/DdrO-like proteins are also present in other bacteria [30,31]. However, questions remain about the number of the genes that are directly or indirectly regulated by these two proteins.…”