TREX1 : three prime repair exonuclease 1
Description
The TREX1 (three prime repair exonuclease 1) is a protein-coding gene located on chromosome 3.
The TREX1 gene provides instructions for making the 3-prime repair exonuclease 1 enzyme. This enzyme is a DNA exonuclease, which means that it trims molecules of DNA by removing DNA building blocks (nucleotides) from the ends of the molecules. In this way, it breaks down unneeded DNA molecules or fragments that may be generated during copying (replication) of cells' genetic material in preparation for cell division. These fragments may also be generated during DNA repair, cell death (apoptosis), and other processes.
TREX1 is a major cellular 3'-to-5' DNA exonuclease that digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini. It plays a crucial role in preventing cell-intrinsic initiation of autoimmunity by metabolizing DNA fragments from endogenous retroelements, including L1, LTR, and SINE elements. TREX1 also degrades DNA fragments at cytosolic micronuclei arising from genome instability, limiting CGAS activation and subsequent inflammation. It prevents chronic ATM-dependent checkpoint activation by processing ssDNA polynucleotide species arising from aberrant DNA replication intermediates. TREX1 inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light. During GZMA-mediated cell death, TREX1 contributes to DNA damage in concert with NME1, removing bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair.
TREX1 is also known as AGS1, CRV, DRN3, HERNS, RVCLS.
Associated Diseases
- Aicardi-Goutières syndrome
- Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations
- Chilblain lupus 1
- Systemic lupus erythematosus
- Vasculopathy, retinal, with cerebral leukodystrophy
- Aicardi-Goutieres syndrome 1
