CRISPR-based genome editing through the lens of DNA repair

Genome editing technologies operate by inducing site-specific DNA perturbations that are resolved by cellular DNA repair pathways. Products of genome editors include DNA breaks generated by CRISPR-associated nucleases, base modifications induced by base editors, DNA flaps created by prime editors, and integration intermediates formed by site-specific recombinases and transposases associated with CRISPR systems. Here, we discuss the cellular processes that repair CRISPR-generated DNA lesions and describe strategies to obtain desirable genomic changes through modulation of DNA repair pathways. Advances in our understanding of the DNA repair circuitry, in conjunction with the rapid development of innovative genome editing technologies, promise to greatly enhance our ability to improve food production, combat environmental pollution, develop cell-based therapies, and cure genetic and infectious diseases. Nambiar et al. review recently developed CRISPR-based technologies, with an emphasis on the DNA lesions generated by these technologies and the DNA repair processes that resolve them. Understanding the interplay between CRISPR-based genome editing and DNA repair will provide strategies to enhance editing efficiency, optimize editing outcomes, and improve safety.