CRISPR-Cas Systems Optimize Their Immune Response by Specifying the Site of Spacer Integration

• Published in: Molecular cell Vol. 64; no. 3; pp. 616 - 623
• Main Authors: McGinn, Jon, Marraffini, Luciano A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03-11-2016
• Subjects: 5' Untranslated Regions; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriophages - immunology; Base Sequence; Chromosomes, Bacterial - chemistry; Clustered Regularly Interspaced Short Palindromic Repeats; CRISPR-Associated Proteins - genetics; CRISPR-Associated Proteins - immunology; CRISPR-Cas Systems - immunology; Endonucleases - genetics; Endonucleases - metabolism; Gene Expression Regulation, Bacterial; Genetic Loci; Staphylococcus aureus - genetics; Staphylococcus aureus - immunology; Staphylococcus aureus - virology; Streptococcus pyogenes - genetics; Streptococcus pyogenes - immunology; Streptococcus pyogenes - virology
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2016.08.038

CRISPR-Cas systems defend prokaryotes against viruses and plasmids. Short DNA segments of the invader, known as spacers, are stored in the CRISPR array as immunological memories. New spacers are added invariably to the 5′ end of the array; therefore, the first spacer matches the latest foreign threat. Whether this highly polarized order of spacer insertion influences CRISPR-Cas immunity has not been explored. Here we show that a conserved sequence located immediately upstream of the CRISPR array specifies the site of new spacer integration. Mutation of this sequence results in erroneous incorporation of new spacers into the middle of the array. We show that spacers added through polarized acquisition give rise to more robust CRISPR-Cas immunity than spacers added to the middle of the array. This study demonstrates that the CRISPR-Cas system specifies the site of spacer integration to optimize the immune response against the most immediate threat to the host.
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•Type II CRISPR spacers are predominantly added to the leader-end of the array•A conserved sequence within the leader specifies the site of spacer integration•Leader mutations lead to spacer insertion at alternate positions within the array•Polarized spacer integration gives rise to a more robust CRISPR immune response
The organization of immunological memories in the CRISPR immune system is tightly controlled. The CRISPR leader specifies the site of spacer integration to prioritize immunity against the latest viral infection, thereby protecting the host against its most immediate threat.