Great Times for Small Molecules: c-di-AMP, a Second Messenger Candidate in Bacteria and Archaea
Great Times for Small Molecules: c-di-AMP, a Second Messenger Candidate in Bacteria and Archaea
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DOI：
10.1126/scisignal.133pe39
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发表时间：
2008-08-19
影响因子：
7.3
通讯作者：
Romling, Ute
中科院分区：
文献类型：
--
作者：
Romling, Ute
在原核生物和真核生物中成功的细胞分裂是通过调节细胞周期进程的检查点来确保的。DNA完整性扫描蛋白（DisA）的结构和生物化学分析最近表明，其功能未知的结构域DUF 147（重命名为DAC（二腺苷酸环化酶））具有二腺苷酸环化酶活性。这种二腺苷酸环化酶的活性被废除时，DisA结合到分支的DNA底物，这在DNA复制过程中自发发生的DNA双链断裂过程中出现。这一发现将环状二（3 '-> 5'）-腺苷酸（c-di-AMP）鉴定为第二信使候选物，其在芽孢形成期间在枯草芽孢杆菌中发出DNA完整性的信号，芽孢形成是一种专门的细胞分裂过程，导致形成称为孢子的休眠细胞。DAC结构域广泛存在于细菌和酵母中;此外，它存在于含有不同结构域的蛋白质中，这表明c-di-AMP作为第二信使分子响应除了分支DNA之外的各种信号。为了阐明c-di-AMP和最近公认的第二信使c-di-GMP的生物学重要性和分子作用机制，将需要多学科的方法。
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.