Cas9 Cleavage of Viral Genomes Primes the Acquisition of New Immunological Memories.

Publication Type Academic Article
Authors Nussenzweig P, McGinn J, Marraffini L
Journal Cell Host Microbe
Volume 26
Issue 4
Pagination 515-526.e6
Date Published 10/01/2019
ISSN 1934-6069
Keywords CRISPR-Cas Systems, DNA, Intergenic, DNA, Viral, RNA, Guide, CRISPR-Cas Systems, Staphylococcus aureus, Streptococcus thermophilus
Abstract Type II CRISPR-Cas systems defend prokaryotes from bacteriophage infection through the acquisition of short viral DNA sequences known as spacers, which are transcribed into short RNA guides to specify the targets of the Cas9 nuclease. To counter the potentially devastating propagation of escaper phages with mutations in the target sequences, the host population acquires many different spacers. Whether and how pre-existing spacers in type II systems affect the acquisition of new ones is unknown. Here, we demonstrate that previously acquired spacers promote additional spacer acquisition from the vicinity of the target DNA site cleaved by Cas9. Therefore, CRISPR immune cells acquire additional spacers at the same time as they destroy the infecting virus. This anticipates the rise of escapers or related viruses that could escape targeting by the first spacer acquired. Our results thus reveal Cas9's role in the generation of immunological memories.
DOI 10.1016/j.chom.2019.09.002
PubMed ID 31585845
PubMed Central ID PMC7558852
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