In response to DNA damage, cells activate checkpoint signaling cascades to control cell-cycle progression and elicit DNA repair in order to maintain genomic integrity. The sensing and repair of lesions is critical for Bacillus subtilis cells entering the developmental process of sporulation as damaged DNA may prevent the cells from completing spore morphogenesis. We report the identification of the protein DisA (DNA integrity scanning protein, annotated YacK), which is required to delay the initiation of sporulation in response to chromosomal damage. DisA is a nonspecific DNA binding protein that forms a single focus, which moves rapidly within the bacterial cell, pausing at sites of DNA damage. We propose that the DisA focus scans along the chromosomes searching for lesions. Upon encountering a lesion, DisA delays entry into sporulation until the damage is repaired.

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SummaryAutoinducer-2 (AI-2) a signal produced by a range of phylogenetically distant microorganisms, enables inter-species cell-cell communication and regulates many bacterial phenotypes. Certain bacteria can interfere with AI-2-regulated behaviours of neighbouring species by internalizing AI-2 using the Lsr transport system (encoded by the lsr operon). AI-2 imported by the Lsr is phosphorylated by the LsrK kinase and AI-2-phosphate is the inducer of the lsr operon. Here we show that in Escherichia coli the phosphoenolpyruvate phosphotransferase system (PTS) is required for Lsr activation and is essential for AI-2 internalization. Although the phosphorylation state of Enzyme I of PTS is important for this regulation, LsrK is necessary for the phosphorylation of AI-2, indicating that AI-2 is not phosphorylated by PTS. Our results suggest that AI-2 internalization is initiated by a PTS-dependent mechanism, which provides sufficient intracellular AI-2 to relieve repression of the lsr operon and, thus induce depletion of AI-2 from the extracellular environment. The fact that AI-2 internalization is not only controlled by the communitydependent accumulation of AI-2, but also depends on the phosphorylation state of PTS suggests that E. coli can integrate information on the availability of substrates with external communal information to control quorum sensing and its interference.

Summary Reducing the activity of the Insulin/IGF-1 Signaling pathway (IIS) modifies development, elevates stress resistance, protects from toxic protein aggregation (proteotoxicity) and extends lifespan of worms, flies and mice. In the nematode Caenorhabditis elegans (C. elegans), lifespan extension by IIS reduction is entirely dependent upon the activity of the transcription factors DAF-16 and the Heat Shock Factor-1 (HSF-1). While DAF-16 determines lifespan exclusively during early adulthood it is required for proteotoxicity protection also during late adulthood. In contrast, HSF-1 protects from proteotoxicity during larval development. Despite the critical requirement for HSF-1 for lifespan extension the temporal requirements for this transcription factor as a lifespan determinant are unknown. To establish the temporal requirements of HSF-1 for longevity assurance we conditionally knocked down hsf-1 during larval development and adulthood of C. elegans and found that unlike daf-16, hsf-1 is foremost required for lifespan determination during early larval development, required for a lesser extent during early adulthood and has small effect on longevity also during late adulthood. Our findings indicate that early developmental events affect lifespan and suggest that HSF-1 sets during development the conditions that enable DAF-16 to promote longevity during reproductive adulthood. This study proposes a novel link between HSF-1 and the longevity functions of the IIS.