Three prime repair exonuclease 2 is an enzyme that in humans is encoded by the TREX2 gene.
This gene encodes a protein with 3' exonuclease activity. Enzymes with this activity are involved in DNA replication, repair, and recombination. Similarity to an E. coli protein suggests that this enzyme may be a subunit of DNA polymerase III, which does not have intrinsic exonuclease activity.
Newer research has determined that TREX2 is also involved in flap endonuclease activity, as detected in the context of inhibiting gene-editing nickases that generate an extension flap such as prime editors that do not usually create a double-stranded break. This function was first demonstrated in a thesis by Lung in 2021, and replicated by Koeppel et al. in 2023. Subsequently, TREX2 has become incorporated into fusion enzymes for genetic engineering by multiple research groups for the purposes of reducing off-target edits which include chromosomal translocations and mismatched insertions.
Mutations in this gene may lead to Aicardi-Goutieres syndrome.
