Editors' ChoiceMicrobiology

Damage Control

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Science Signaling  29 Apr 2008:
Vol. 1, Issue 17, pp. ec151
DOI: 10.1126/stke.117ec151

In the soil bacterium Bacillus subtilis, the checkpoint protein DisA (DNA integrity scanning protein A) scans the bacterial chromosome at the onset of sporulation; it localizes at sites of DNA damage to temporarily block sporulation and allow the bacterium to repair the damage before proceeding. Witte et al. performed structural analysis of Thermotoga maritima DisA and determined that it formed an octameric complex; intriguingly, they found bis-(3′,5′)-cyclic dimeric adenosine monophosphate (c-di-AMP) bound to the purified complex. When nucleotide-deprived DisA was crystallized in the presence of Mg2+-ATPγS, the crystals were again bound to c-di-AMP, indicating that DisA could act as a diadenylate cyclase. c-di-GMP is known to act as a signaling molecule in bacteria; however, fluorescence anisotropy titration analysis revealed that the binding affinity of fluorescently labeled ATP for both T. maritima and B. subtilis DisA was about 20 times greater than that of fluorescently labeled GTP. Furthermore, nucleotide cyclase assays revealed that both T. maritima and B. subtilis DisA converted ATP to c-di-AMP but did not convert GTP to c-di-GMP. DisA thus appears to be the first protein identified with specific diadenylate cyclase activity. Although neither single-stranded nor double-stranded DNA affected DisA cyclase activity, branched DNA bound to DisA and inhibited its cyclase activity. The authors thus propose that DisA uses c-di-AMP to signal the existence of structures that would interfere with chromosomal segregation, allowing c-di-AMP to join the list of naturally occurring purine-based signaling nucleotides.

G. Witte, S. Hartung, K. Büttner, K.-P. Hopfner, Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates. Mol. Cell 30, 167-178 (2008). [PubMed]

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