Three prime repair exonuclease 1 is an enzyme that in humans is encoded by the TREX1 gene.[5][6][7][8]

TREX1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTREX1, AGS1, CRV, DRN3, HERNS, three prime repair exonuclease 1, RVCLS
External IDsOMIM: 606609; MGI: 1328317; HomoloGene: 7982; GeneCards: TREX1; OMA:TREX1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_033629
NM_007248
NM_016381
NM_033627
NM_033628

NM_001012236
NM_011637

RefSeq (protein)

NP_009179
NP_338599

NP_001012236
NP_035767

Location (UCSC)Chr 3: 48.47 – 48.47 MbChr 9: 108.89 – 108.89 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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This gene encodes the major 3'->5' DNA exonuclease in human cells. The protein is a non-processive exonuclease that may serve a proofreading function for a human DNA polymerase. It is also a component of the SET complex, and acts to rapidly degrade 3' ends of nicked DNA during granzyme A-mediated cell death. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, RVCL (Retinal Vasculopathy with Cerebral Leukodystrophy), and Cree encephalitis. Multiple transcript variants encoding different isoforms have been found for this gene.[8]

Clinical relevance

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Mutations within the TREX1 gene cause familial chilblain lupus. The TREX1 polymorphisms confer susceptibility to systemic lupus erythematosus. Missense mutations of the TREX1 gene significantly downregulate its exonucleolytic capacity and result in the accumulation of nucleic acids. The build-up of the nucleic acids within the cytoplasm stimulates type-I interferon responses that could trigger autoimmune responses.[9] The region containing the TREX1 gene (3p21.31) has been linked to COVID-19 severity in a recent genome-wide association study.[10] This might explain the occurrence of chilblain like lesions in patients infected with SARS-CoV-2.[9]

TREX1 helps HIV‑1 to evade cytosolic sensing by degrading viral cDNA in the cytoplasm[11]

Mutations in TREX1 can give cause failure to appropriately remove ribonucleotides misincorporated into DNA.[12] The removal process is ordinary performed by ribonucleotide excision repair. In humans, a defect in this process can give rise to Aicardi-Goutieres syndrome involving microcephaly and neuroinflammation.[12]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000213689Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049734Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Mazur DJ, Perrino FW (Aug 1999). "Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'-->5' exonucleases". J Biol Chem. 274 (28): 19655–60. doi:10.1074/jbc.274.28.19655. PMID 10391904.
  6. ^ Hoss M, Robins P, Naven TJ, Pappin DJ, Sgouros J, Lindahl T (Aug 1999). "A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein". EMBO J. 18 (13): 3868–75. doi:10.1093/emboj/18.13.3868. PMC 1171463. PMID 10393201.
  7. ^ Crow YJ, Hayward BE, Parmar R, Robins P, Leitch A, Ali M, Black DN, van Bokhoven H, Brunner HG, Hamel BC, Corry PC, Cowan FM, Frints SG, Klepper J, Livingston JH, Lynch SA, Massey RF, Meritet JF, Michaud JL, Ponsot G, Voit T, Lebon P, Bonthron DT, Jackson AP, Barnes DE, Lindahl T (Jul 2006). "Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus". Nat Genet. 38 (8): 917–20. doi:10.1038/ng1845. PMID 16845398. S2CID 9069106.
  8. ^ a b "Entrez Gene: TREX1 three prime repair exonuclease 1".
  9. ^ a b Jabalameli, Navid (2021). "Overlap between Genetic Susceptibility to COVID-19 and Skin Diseases". Immunological Investigations. 51 (4): 1087–94. doi:10.1080/08820139.2021.1876086. PMID 33494631.
  10. ^ Ellinghaus (2020). "Genomewide Association Study of Severe Covid-19 with Respiratory Failure". New England Journal of Medicine. 383 (16): 1522–34. doi:10.1056/NEJMoa2020283. PMC 7315890. PMID 32558485.
  11. ^ Doyle, Thomas (27 April 2015). "HIV-1 and interferons: who's interfering with whom?". Nature Reviews Microbiology. 13 (Nature Reviews Microbiology 13): 403–413. doi:10.1038/nrmicro3449. PMC 7768976. PMID 25915633. S2CID 205499122.
  12. ^ a b McKinnon PJ (June 2017). "Genome integrity and disease prevention in the nervous system". Genes Dev. 31 (12): 1180–94. doi:10.1101/gad.301325.117. PMC 5558921. PMID 28765160.

Further reading

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