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Sci. Signal., 19 August 2008
Vol. 1, Issue 33, p. pe39
[DOI: 10.1126/scisignal.133pe39]


Great Times for Small Molecules: c-di-AMP, a Second Messenger Candidate in Bacteria and Archaea

Ute Römling*

Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology, FE280, SE-171 77 Stockholm, Sweden.

Abstract: Successful cell division in pro- and eukaryotes is ensured by checkpoints that regulate cell cycle progression. Structural and biochemical analyses of the DNA integrity scanning protein (DisA) have recently shown that its domain of unknown function, DUF147 [renamed DAC (for diadenylate cyclase)], has diadenylate cyclase activity. This diadenylate cyclase activity is abolished when DisA binds to branched DNA substrates, which arise during DNA double-strand breaks that can spontaneously occur during DNA replication. This finding identifies cyclic di(3'->5')-adenylic acid (c-di-AMP) as a second messenger candidate that signals DNA integrity in Bacillus subtilis during sporulation, a specialized cell division process that leads to formation of a dormant cell called a spore. The DAC domain is widespread in Bacteria and Archaea; moreover, it is found in proteins containing diverse domains, suggesting that c-di-AMP acts as a second messenger molecule in response to various signals besides branched DNA. To elucidate the biological importance and molecular mechanisms of action for c-di-AMP and the recently recognized second messenger c-di-GMP will require a multidisciplinary approach.

*Corresponding author. E-mail, ute.romling{at}

Citation: U. Römling, Great Times for Small Molecules: c-di-AMP, a Second Messenger Candidate in Bacteria and Archaea. Sci. Signal. 1, pe39 (2008).

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