Cleavage of viral DNA by restriction endonucleases stimulates the type II CRISPR-Cas immune response.
Cleavage of viral DNA by restriction endonucleases stimulates the type II CRISPR-Cas immune response.
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DOI：
10.1016/j.molcel.2022.01.012
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发表时间：
2022-03-03
期刊：
影响因子：
16
通讯作者：
Marraffini LA
中科院分区：
文献类型：
--
作者：
Maguin P;Varble A;Modell JW;Marraffini LA
原核生物已经开发出多种针对噬菌体的防御系统，但对这些系统是否相互作用以及如何相互作用知之甚少。在这里，我们研究了两个最重要的原核免疫系统之间的联系：限制性内切酶修饰和CRISPR。虽然这两个系统都使用酶来裂解入侵者的特定DNA序列，但CRISPR核酸酶是用噬菌体衍生的间隔区序列编程的，这些间隔区序列在感染时整合到CRISPR基因座。我们发现，限制性内切酶提供了一种短期防御，这种防御可以通过噬菌体基因组的甲基化迅速克服。然而，在一小部分细胞中，限制导致从裂解位点获得间隔区序列，这介导了针对甲基化噬菌体的强大的II-A型CRISPR-Cas免疫反应。这种机制让人联想到真核免疫，在真核免疫中，先天反应提供了第一道临时防线，也激活了第二条更强大的适应性反应。限制性和CRISPR-Cas核酸酶裂解噬菌体DNA。Maguin等人。展示它们是如何协调起来的，以保护细菌免受感染。限制性内切酶为CRISPR-CAS系统获得间隔区提供初始保护并产生游离dsDNA末端。间隔物引导CRISPR核酸酶破坏甲基化的噬菌体DNA，绕过限制。
Prokaryotic organisms have developed multiple defense systems against phages, however little is known about whether and how these interact with each other. Here we studied the connection between two of the most prominent prokaryotic immune systems: restriction-modification and CRISPR. While both systems employ enzymes that cleave a specific DNA sequence of the invader, CRISPR nucleases are programmed with phage-derived spacer sequences, which are integrated into the CRISPR locus upon infection. We found that restriction endonucleases provide a short-term defense that is rapidly overcome through methylation of the phage genome. In a small fraction of the cells, however, restriction results in acquisition of spacer sequences from the cleavage site, which mediates a robust type II-A CRISPR-Cas immune response against the methylated phage. This mechanism is reminiscent of eukaryotic immunity, where the innate response offers a first temporary line of defense, and also activates a second and more robust adaptive response. Restriction and CRISPR-Cas nucleases cleave phage DNA. Maguin et al. show how these are coordinated to defend bacteria from infection. Restriction provides initial protection and also generates free dsDNA ends for the acquisition of spacers by CRISPR-Cas systems. Spacers guide CRISPR nucleases to destroy methylated phage DNA that bypasses restriction.
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影响因子：
64.8
作者：
Goldberg, Gregory W.;Jiang, Wenyan;Bikard, David;Marraffini, Luciano A.
通讯作者：
Marraffini, Luciano A.
影响因子：
14.9
作者：
Jakhanwal S;Cress BF;Maguin P;Lobba MJ;Marraffini LA;Doudna JA
通讯作者：
Doudna JA
影响因子：
46.9
作者：
Bikard, David;Euler, Chad W.;Jiang, Wenyan;Nussenzweig, Philip M.;Goldberg, Gregory W.;Duportet, Xavier;Fischetti, Vincent A.;Marraffini, Luciano A.
通讯作者：
Marraffini, Luciano A.
影响因子：
3.2
作者：
Deveau, Helene;Barrangou, Rodolphe;Moineau, Sylvain
通讯作者：
Moineau, Sylvain
影响因子：
16.6
作者：
Dupuis, Marie-Eve;Villion, Manuela;Moineau, Sylvain
通讯作者：
Moineau, Sylvain