title: DisA and c-di-AMP act at the intersection between DNA-damage response and stress homeostasis in exponentially growing Bacillus subtilis cells.
abstract: Bacillus subtilis contains two vegetative diadenylate cyclases, DisA and CdaA, which produce cyclic di-AMP (c-di-AMP), and one phosphodiesterase, GdpP, that degrades it into a linear di-AMP. We report here that DisA and CdaA contribute to elicit repair of DNA damage generated by alkyl groups and H2O2, respectively, during vegetative growth. disA forms an operon with radA (also termed sms) that encodes a protein distantly related to RecA. Among different DNA damage agents tested, only methyl methane sulfonate (MMS) affected disA null strain viability, while radA showed sensitivity to all of them. A strain lacking both disA and radA was as sensitive to MMS as the most sensitive single parent (epistasis). Low c-di-AMP levels (e.g. by over-expressing GdpP) decreased the ability of cells to repair DNA damage caused by MMS and in less extent by H2O2, while high levels of c-di-AMP (absence of GdpP or expression of sporulation-specific diadenylate cyclase, CdaS) increased cell survival. Taken together, our results support the idea that c-di-AMP is a crucial signalling molecule involved in DNA repair with DisA and CdaA contributing to modulate different DNA damage responses during exponential growth.
authors.affiliation: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gándara
authors.affiliation: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Madrid, Spain. Electronic address: jcalonso@cnb.csic.es.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Alonso
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004269:DNA, Bacterial / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D055785:Gene Knockdown Techniques; D006706:Homeostasis; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D019761:Phosphorus-Oxygen Lyases / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D000477:Alkylating Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; C100901:RadA protein, bacteria; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D019761:Phosphorus-Oxygen Lyases
keywords: DNA damage response; Double strand break; RadA; Single-strand gap; Sms