Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv 69978, Israel.
Nucleic Acids Res. 2014 Jan;42(1):328-39. doi: 10.1093/nar/gkt851. Epub 2013 Sep 22.
Double-stranded DNA breaks (DSB) cause bacteria to augment expression of DNA repair and various stress response proteins. A puzzling exception educes the anticodon nuclease (ACNase) RloC, which resembles the DSB responder Rad50 and the antiviral, translation-disabling ACNase PrrC. While PrrC's ACNase is regulated by a DNA restriction-modification (R-M) protein and a phage anti-DNA restriction peptide, RloC has an internal ACNase switch comprising a putative DSB sensor and coupled ATPase. Further exploration of RloC's controls revealed, first, that its ACNase is stabilized by the activating DNA and hydrolysed nucleotide. Second, DSB inducers activated RloC's ACNase in heterologous contexts as well as in a natural host, even when R-M deficient. Third, the DSB-induced activation of the indigenous RloC led to partial and temporary disruption of tRNA(Glu) and tRNA(Gln). Lastly, accumulation of CRISPR-derived RNA that occurred in parallel raises the possibility that the adaptive immunity and RloC provide the genotoxicated host with complementary protection from impending infections.
双链 DNA 断裂 (DSB) 会促使细菌增强 DNA 修复和各种应激反应蛋白的表达。一个令人费解的例外是反密码子核酸酶 (ACNase) RloC，它类似于 DSB 应答蛋白 Rad50 和抗病毒、翻译失活的 ACNase PrrC。虽然 PrrC 的 ACNase 受到 DNA 限制修饰 (R-M) 蛋白和噬菌体抗 DNA 限制肽的调控，但 RloC 具有内部 ACNase 开关，包括一个假定的 DSB 传感器和偶联的 ATP 酶。对 RloC 控制的进一步探索表明，首先，其 ACNase 被激活的 DNA 和水解核苷酸稳定。其次，DSB 诱导剂在异源环境以及在自然宿主中激活 RloC 的 ACNase，即使 R-M 缺失也是如此。第三，内源性 RloC 的 DSB 诱导激活导致 tRNA(Glu) 和 tRNA(Gln) 的部分和暂时破坏。最后，与 CRISPR 相关的 RNA 的积累平行发生，这增加了适应性免疫和 RloC 为受到遗传毒性的宿主提供互补保护以抵御即将到来的感染的可能性。
