The signal transduction mechanisms
in response to nutritional stress and other abiotic stresses besides DNA damage have been shown in bacteria (Parkinson, 1993). In this study, we highlight, for the first time, the presence of a γ radiation-induced signaling mechanism in a prokaryote, D. radiodurans. We demonstrate that the DNA damage-induced synthesis of cAMP and ATP was possibly manifested by upregulation of AC and downregulation of 2′,3′ cAMP phosphodiesterase activities during PIR. The presence of different ACs and their involvement in bacterial signal transduction are well established (Linder & Schultz, 2003; Shenoy & Visweswariah, 2006). Although, the mechanism by which cAMP regulates DNA damage response is not clear; it can presumably act as an inducer of protein kinase Epacadostat activity and a signaling molecule in bacteria, as is known in eukaryotes (De Gunzburg, 1985). Similarly, the effects of DNA damage and oxidative stress on AC and 2′,3′cyclic phosphodiesterase enzymes have not INNO-406 been studied, but the regulation of cyclic phosphodiesterase and AC activities by a membrane receptor relaxin-mediated tyrosine phosphorylation has been demonstrated in mammalian cells (Bartsch et al., 2001). As cAMP is a
known activator of mitogen-activated protein kinases and other soluble as well as membrane-bound protein kinases (Stork & Schmitt, 2002; Sanz, 2008) in eukaryotes, it is likely that the higher levels of cAMP and AC activity in 1- and 0.5-h PIR samples, Pregnenolone respectively, regulate protein phosphorylation in this bacterium by similar mechanisms. Our results show that (1) the levels of cAMP and ATP change in response to DNA damage, possibly manifested by differential regulation of AC and cyclic phosphodiesterase enzymes and (2) DNA damage-inducible protein kinase-mediated ATP attenuation of nucleolytic activity is involved during PIR. This is consistent with the activation
of protein kinase by DNA damage in eukaryotes (Kitagawa & Kastan, 2005). Thus, there exists a DSB-induced signaling mechanism in this extremophile, which is known to have acquired the genetic elements from higher organisms through horizontal gene transfer (Makarova et al., 2001; Blasius et al., 2008). The possibility that this superbug has acquired the DNA damage-induced signaling pathway from other organisms during evolution cannot be ruled out and would be worth investigating. We express our sincere thanks to Dr S.K. Apte, Bhabha Atomic Research Centre, Mumbai, for the technical and critical comments in data interpretation and in the preparation of the manuscript. Prof. S.P. Modak, Pune University, and Ms Swathi Kota, Bhabha Atomic Research Centre, are thanked for their comments on scientific and technical aspects of the manuscript. “
“We agree with the authors that the maintenance of patients in care and, where appropriate, on treatment after diagnosis is vital for their continued good health.