4.6 Review Book Chapter

Molecular Mechanisms of CRISPR-Cas Immunity in Bacteria

Journal

ANNUAL REVIEW OF GENETICS, VOL 54, 2020
Volume 54, Issue -, Pages 93-120

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev-genet-022120-112523

Keywords

CRISPR-Cas; phage defense; adaptive immunity; RNA; CRISPR targeting; spacer acquisition

Funding

  1. National Institutes of Health (NIH) Medical Scientist Training Program [T32GM07739]
  2. Burroughs Wellcome Fund PATH Award
  3. NIH Director's Pioneer Award [DP1GM128184]

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Prokaryotes have developed numerous defense strategies to combat the constant threat posed by the diverse genetic parasites that endanger them. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas loci guard their hosts with an adaptive immune system against foreign nucleic acids. Protection starts with an immunization phase, in which short pieces of the invader's genome, known as spacers, are captured and integrated into the CRISPR locus after infection. Next, during the targeting phase, spacers are transcribed into CRISPR RNAs (crRNAs) that guide CRISPR-associated (Cas) nucleases to destroy the invader's DNA or RNA. Here we describe the many different molecular mechanisms of CRISPR targeting and how they are interconnected with the immunization phase through a third phase of the CRISPR-Cas immune response: primed spacer acquisition. In this phase, Cas proteins direct the crRNA-guided acquisition of additional spacers to achieve a more rapid and robust immunization of the population.

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