Three prime repair exonuclease 2 (TREX2)

Three prime repair exonuclease 2 (TREX2) is an enzyme encoded by the TREX2 gene in humans, functioning as a 3'-5' exonuclease involved in the maintenance of genome integrity. It is essential for precise processing of DNA ends during repair, particularly removing mismatched 3’ termini from duplex DNA. TREX2 acts as a homodimer and its activity is necessary for efficient DNA binding, catalytic processing, and subsequent genome maintenance. Structural studies demonstrate that it specifically trims 3'-overhangs from DNA, ensuring accurate DNA repair and minimizing unwanted genomic alterations. TREX2 is ubiquitously expressed in human and mouse tissues and is regulated during the cell cycle, with reduced levels at the G2/M phase. Disruption of TREX2 function impairs cell proliferation and increases susceptibility to DNA damage, underlying its relevance in disease contexts such as cancer and Aicardi-Goutieres syndrome. TREX2, through its association with the TREX-2 complex, also plays a role (albeit indirectly) in mRNA export and nuclear architecture organization. While not currently a direct drug target, it is exploited in gene-editing research to enhance fidelity and minimize harmful editing outcomes.

Other names

Three-prime repair exonuclease 23'-5' exonuclease TREX23'-5' exonuclease TREX2 long formTREX2L1TREX2L2TREX-2TREX2 protein3' exonuclease

For engineered gene-editing enzymes: Fusion of TREX2 to Cas9 or other genome editing tools increases editing efficiency or alters editing outcomes by its 3'-5' exonuclease activity (removal of overhangs or processing DNA ends). No approved pharmacological mechanism as a drug target in humans as of now.