non-homologous end joining

Non-homologous end joining is the cell's fast, no-template way to patch a broken chromosome — like taping two snapped rope ends back together without checking whether the join is perfect. It is quick and works at any time, but it is not fussy about getting the sequence exactly right.

When DNA suffers a double-strand break, this pathway grabs the two free ends and ligates them directly, without using a matching template to guide the repair. Often the join is seamless, but the ends may first be trimmed or filled, leaving small insertions or deletions at the seam. Because it needs no homologous copy, it operates throughout the cell cycle and is the predominant repair route in most human cells.

In genome editing, this very imperfection is useful. A cut made by Cas9 and rejoined by end joining frequently gains a few extra or missing bases; inside a gene's coding region, that shifts the reading frame and disables the gene, which is the usual basis of a CRISPR knockout. The same sloppiness is a liability when a precise edit is wanted, since it competes with the accurate homology-directed pathway.