homology-directed repair

Homology-directed repair is the cell's careful, copy-from-a-backup way of fixing a broken chromosome. When DNA snaps, instead of crudely gluing the ends together, the cell finds a matching, undamaged sequence and uses it as a template — like restoring a torn page by copying from an intact second copy of the book.

After a double-strand break, the cell can use a homologous template — normally the sister chromatid or the other homologous chromosome — to rebuild the missing sequence exactly. The broken end is trimmed, finds the matching region, and DNA synthesis copies across the template, restoring the original sequence without errors. This is closely related to the homologous recombination that shuffles genes during meiosis.

Genome editors hijack this pathway for precision. By supplying an artificial repair template carrying a desired change, scientists can make the cell copy in an exact edit — a corrected base or an inserted gene — rather than a random scar. The catch is that homology-directed repair mostly operates in dividing cells and is often less efficient than the competing, error-prone end-joining pathway.