CRISPR-Cas adaptation in Escherichia coli

Prokaryotes use the adaptive immunity mediated via the Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR associated (CRISPR-Cas) system for protection against invading elements such as phages and plasmids. The immunity is achieved by cap-turing small DNA fragments or spacers from foreign nucleic acids (protospacers) and inte-grating them into the host CRISPR locus. This step of CRISPR-Cas immunity called nave CRISPR adaptation requires the conserved Cas1-Cas2 complex and is often supported by variable host proteins that assist in spacer processing and integration. Bacteria that have acquired new spacers become immune to the same invading elements when reinfected. CRISPR-Cas immunity can also be updated by integrating new spacers from the same in-vading elements, a process called primed adaptation. Only properly selected and inte-grated spacers are functional in the next steps of CRISPR immunity when their processed transcripts are used for RNA-guided target recognition and interference (target degrada-tion). Capturing, trimming, and integrating new spacers in the correct orientation are uni-versal steps of adaptation to all CRISPR-Cas systems, but some details are CRISPR-Cas type-specific and species-specific. In this review, we provide an overview of the mecha-nisms of CRISPR-Cas class 1 type I-E adaptation in Escherichia coli as a general model for adaptation processes (DNA capture and integration) that have been studied in detail. We focus on the role of host non-Cas proteins involved in adaptation, particularly on the role of homologous recombination.