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nature portfolio permissions reprints european research council privacy policy provide additional tools research excellence advertising pam-dependent spacer acquisition double-stranded endonuclease activity crispr/cas spacer acquisition social media double-stranded dna breaks crispr-cas immune system crispr-cas protein complex specific crispr–cas components crispr-cas immune systems integrase-mediated spacer acquisition crispr-cas surveillance complexes prokaryotic crispr-cas immunity nature 471 nature 519 nature 527 nature 520 nature crispr–cas adaptation machinery author information authors crispr–cas adaptive immunity single rna-guided endonuclease crispr-mediated genome defense author correspondence double-strand breaks host-derived crispr spacers trans-encoded small rna vivo-generated cruciform structures crispr–cas system crispr/cas system crispr–cas systems crispr-cas systems progress article personal data spacer integration intermediates crispr–cas adaptation springerlink instant access data protection permissions adaptive immune systems cas1 integrase directs anti-phage immunity mechanisms cas protein families single-strand interruptions

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         description:Although the mechanisms of CRISPR–Cas interference have largely been elucidated, how new sequence memories are stored had remained unknown. In this Progress article, Amitai and Sorek discuss recent advances in the study of this adaptation stage of CRISPR immunity. Since the first demonstration that CRISPR–Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR–Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR–Cas components that are involved in memory formation, and consider current models for their evolutionary origin.
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      headline:CRISPR–Cas adaptation: insights into the mechanism of action
      description:Although the mechanisms of CRISPR–Cas interference have largely been elucidated, how new sequence memories are stored had remained unknown. In this Progress article, Amitai and Sorek discuss recent advances in the study of this adaptation stage of CRISPR immunity. Since the first demonstration that CRISPR–Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR–Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR–Cas components that are involved in memory formation, and consider current models for their evolutionary origin.
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