homologydirected

Homology-directed repair is a cellular DNA repair pathway that restores damaged DNA using a homologous sequence as a template. It is contrasted with non-homologous end joining, which directly ligates broken ends and often introduces small insertions or deletions. HDR tends to be high fidelity when a suitable template is available.

The process relies on a donor DNA template bearing regions of sequence homology to the site of a double-strand break. After the break is recognized, the repair machinery uses the homologous regions to guide accurate DNA synthesis and incorporate the template sequence into the genome. HDR typically requires the cell to be in a phase of the cell cycle in which a homologous template is present, such as S or G2.

In genome editing, programmable nucleases—such as CRISPR-Cas9, TALENs, or zinc finger nucleases—are used to create targeted double-strand breaks. Providing a donor template with desired modifications allows precise edits, including sequence changes, insertions, or tag insertions at a specific genomic locus. HDR-based editing competes with NHEJ, and efficiency is often limited, varying by cell type and context.

Applications of homology-directed repair include the precise correction of mutations, targeted gene insertion or replacement, and the introduction of reporter tags for functional studies. In research and therapeutic settings, HDR enables more exact genome modifications than methods relying on error-prone repair, though challenges such as low efficiency, mosaicism, and delivery considerations remain significant.

See also: genome editing, non-homologous end joining, gene replacement, donor DNA, homology arms.