Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini ( ). Prevents cell-intrinsic initiation of autoimmunity ( ). Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements ( ). Plays a key role in degradation of DNA fragments at cytosolic micronuclei arising from genome instability: its association with the endoplasmic reticulum membrane directs TREX1 to ruptured micronuclei, leading to micronuclear DNA degradation . Micronuclear DNA degradation is required to limit CGAS activation and subsequent inflammation . Unless degraded, these DNA fragments accumulate in the cytosol and activate the cGAS-STING innate immune signaling, leading to the production of type I interferon . Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates . Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light . During GZMA-mediated cell death, contributes to DNA damage in concert with NME1 . NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair .
Subcellular locations: Nucleus, Cytoplasm, Cytosol, Endoplasmic reticulum membrane
Retained in the cytoplasm through the C-terminal region (By similarity). Localization to the endoplasmic reticulum membrane is required to direct TREX1 to ruptured micronuclei . In response to DNA damage, translocates to the nucleus where it is specifically recruited to replication foci . Translocation to the nucleus also occurs during GZMA-mediated cell death .
Detected in thymus, spleen, liver, brain, heart, small intestine and colon.