What are the two main types of DNA repair mechanisms employed in CRISPR-Cas9?

The two main types of DNA repair mechanisms that are employed in CRISPR-Cas9 are non-homologous end joining (NHEJ) and homology-directed repair (HDR).

• Non-homologous end joining (NHEJ): The NHEJ mechanism can be exploited when the experimental objective is to permanently disrupt a gene. NHEJ directly ligates the broken DNA ends back together without the need for a homologous template, hence “non-homologous”. Imprecise repair may lead to inserting or deleting nucleotides, which can result in a frameshift mutation and likely terminate the resulting protein’s function.
• Homology-directed repair (HDR): HDR can replace the targeted genetic element with a different sequence, which can only be used by the cell when there is a homologous piece of DNA present. Hence, a DNA donor template bearing the desired sequenced needs to be introduced along with the CRISPR components to the cells. The cells can then use the template to repair the broken ends and incorporate the desired changes into the target region.