| 1999 |
TREX1 encodes a 304-amino acid protein with three conserved motifs generating the exonuclease active site, most closely related to proofreading exonucleases of bacterial replicative DNA polymerases. Recombinant TREX1 expressed in E. coli is an active 3'→5' DNA exonuclease with greatest activity on partial duplex DNA containing 3' mismatched nucleotides; no activity was detected on single-stranded RNA or RNA-DNA partial duplexes. |
Recombinant protein expression in E. coli, in vitro exonuclease activity assays with ssDNA, partial duplex, and mispaired oligonucleotide substrates |
The Journal of biological chemistry |
High |
10391904
|
| 2001 |
TREX1 (mouse) exists as a homodimer with robust 3'→5' exonuclease activity. Steady-state kinetics on ssDNA oligonucleotides yielded kcat ~22 s⁻¹ and KM ~19 nM for mouse Trex1. Competition assays with heparin and partial duplex DNA substrates established substrate structure preferences for 3' nucleotide excision. |
Recombinant protein expression and purification from E. coli, steady-state kinetic analysis, heparin competition assays |
The Journal of biological chemistry |
High |
11279105
|
| 2004 |
Gene-targeted Trex1⁻/⁻ mice are viable but develop inflammatory myocarditis leading to cardiomyopathy and circulatory failure, establishing that TREX1 loss-of-function in vivo causes inflammatory disease rather than increased mutation frequency or cancer. |
Gene targeting (knockout mice), histopathology, survival analysis |
Molecular and cellular biology |
High |
15254239
|
| 2006 |
TREX1 is the major mammalian 3'→5' DNA exonuclease encoded by AGS1; AGS-causing mutations abrogate TREX1 enzyme activity, and similar loss-of-function in Trex1⁻/⁻ mice leads to an inflammatory phenotype, implicating TREX1 in processing or clearing anomalous DNA structures to prevent innate immune triggering. |
Mutational analysis, exonuclease activity assays of patient-derived mutations, Trex1⁻/⁻ mouse model |
Nature genetics |
High |
16845398
|
| 2006 |
TREX1 (but not TREX2) is a component of the endoplasmic reticulum-associated SET complex. TREX1 binds SET, colocalizes and translocates with the SET complex to the nucleus during granzyme A-mediated apoptosis, where it works in concert with NM23-H1 to degrade genomic DNA: after NM23-H1 nicks DNA, TREX1 removes nucleotides from the nicked 3' end. Silencing TREX1 inhibits DNA damage and cell death in response to perforin/granzyme A but not perforin/granzyme B. |
Co-immunoprecipitation, colocalization by immunofluorescence, siRNA knockdown, cell death assays with perforin/granzyme A treatment |
Molecular cell |
High |
16818237
|
| 2007 |
Crystal structure of dimeric mouse TREX1 in substrate and product complexes with ssDNA and deoxyadenosine monophosphate reveals specific active-site interactions with the 3'-terminal nucleotide, providing molecular basis for specificity. Three AGS-associated TREX1 mutants show 4–35,000-fold reduced enzyme activity. The structure reveals an 8-amino acid polyproline II helix on the surface suggesting a mechanism for interactions with other protein complexes. |
X-ray crystallography, site-directed mutagenesis, in vitro exonuclease activity assays |
The Journal of biological chemistry |
High |
17293595
|
| 2007 |
Crystal structures of dimeric murine TREX1 complexed with a nucleotide product and ssDNA substrate reveal sequence preferences for certain DNA motifs (GAG, ACA, CTGC). A conserved proline-rich region (PPPVPRPP) on the TREX1 surface interacts with WW2 domain of transcription elongation factor CA150, confirmed by NMR titration and co-immunoprecipitation with full-length TREX1. Nuclear localization of TREX1 requires loss of a C-terminal segment (leucine-rich repeat 3). |
X-ray crystallography, NMR titration, co-immunoprecipitation, confocal microscopy |
The Journal of biological chemistry |
High |
17355961
|
| 2007 |
TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis. A heterozygous D18N mutation in TREX1 renders recombinant mutant TREX1 homodimers enzymatically inactive; wild-type/D18N heterodimers retain residual activity. Lymphoblastoid cells with D18N are significantly less sensitive to granzyme A-mediated cell death. |
Recombinant protein preparation, in vitro exonuclease activity assays, granzyme A cell death assays in patient-derived lymphoblastoid cells |
Journal of molecular medicine |
High |
17440703
|
| 2007 |
TREX1 is an essential negative regulator of the IFN-stimulatory DNA (ISD) response. In Trex1-deficient cells, single-stranded DNA derived from endogenous retroelements accumulates. TREX1 can metabolize reverse-transcribed DNA, preventing chronic activation of innate immune signaling. Genetic pathway analysis links Trex1 deficiency to lethal autoimmunity through the ISD pathway. |
Genetic screen, Trex1⁻/⁻ mouse cells, ISD pathway reporter assays, DNA accumulation analysis, epistasis via Trex1 KO rescue experiments |
Cell |
High |
18724932
|
| 2007 |
Dominant mutations in TREX1 (D200N and D18N) associated with autoimmune disease exhibit completely deficient dsDNA degradation activity while retaining partial ssDNA degradation activity. The dominant mutant heterodimers (WT/D200N and WT/D18N) inhibit the dsDNA degradation activity of WT TREX1 enzyme, explaining the dominant phenotype. The recessive R114H homodimer has dysfunctional dsDNA and ssDNA activities but does not inhibit WT enzyme. |
In vitro exonuclease activity assays with nicked dsDNA and ssDNA substrates using recombinant homo- and heterodimers |
The Journal of biological chemistry |
High |
18805785
|
| 2007 |
Trex1, ordinarily associated with the endoplasmic reticulum, relocalizes to the S-phase nucleus after gamma irradiation or hydroxyurea treatment. Trex1-deficient cells show chronic ATM-dependent checkpoint activation even without exogenous stress, correlated with persistent ssDNA produced in S phase accumulating in the ER. Trex1 degrades ssDNA arising from aberrant replication intermediates to prevent chronic checkpoint signaling. |
Immunofluorescence/subcellular fractionation, gamma irradiation, hydroxyurea treatment, ATM inhibition, Trex1⁻/⁻ cells |
Cell |
High |
18045533
|
| 2008 |
X-ray crystal structures of TREX1 apoprotein, dominant AGS/FCL mutants (D200H, D200N, D18N) and recessive mutant (V201D) reveal mechanism of catalytic impairment: D200H and D200N lose coordination of one active-site metal and the catalytic histidine (H195) is trapped in a non-catalytic conformation; D18N and V201D bind both metals but with inter-metal distances non-optimal for catalysis. All mutants show reduced mobility of catalytic histidine. |
X-ray crystallography of multiple mutant TREX1 proteins |
DNA repair |
High |
22071149
|
| 2008 |
Lithium and sodium cations inhibit TREX1 exonuclease activity by competing with catalytic magnesium/manganese for the two metal-binding sites, inducing subtle active-site rearrangements. X-ray structures with Li⁺ and Na⁺ in complex with a nucleotide product explain this inhibition mechanism. Mutagenesis of His124 (highly conserved in DEDDh family) confirmed its requirement for TREX1 activity, identifying it as a catalytic residue. |
X-ray crystallography at 2.1 Å and 2.3 Å, in vitro exonuclease activity assays, site-directed mutagenesis of His124 |
Protein science |
High |
18780819
|
| 2010 |
The cytosolic exonuclease TREX1 suppresses interferon triggered by HIV-1 infection. TREX1 binds cytosolic HIV DNA and degrades excess HIV DNA that would otherwise activate type I interferon via a TBK1/STING/IRF3-dependent pathway. In Trex1⁻/⁻ mouse cells and TREX1-knockdown human CD4⁺ T cells and macrophages, cytosolic HIV DNA accumulates and HIV infection induces type I interferon that inhibits HIV replication. |
Trex1⁻/⁻ mouse cells, siRNA knockdown in human T cells/macrophages, co-immunoprecipitation of TREX1 with HIV DNA, interferon induction assays |
Nature immunology |
High |
20871604
|
| 2010 |
TREX1 expression is induced by genotoxic stress (UV light, benzo(a)pyrene, hydrogen peroxide) through an AP-1-dependent transcriptional mechanism. The mouse and human trex1 promoters contain AP-1 binding sites recognized by c-Fos and c-Jun; mutational inactivation of the AP-1 site abolishes induction. Upon genotoxic stress, TREX1 also translocates to the nucleus. TREX1-deficient cells show reduced recovery from UV/benzo(a)pyrene-induced replication inhibition. |
RT-PCR, promoter reporter assays, EMSA, c-fos/c-jun null cells, siRNA knockdown, immunofluorescence localization |
Nucleic acids research |
High |
20511593
|
| 2011 |
TREX1 degrades plasmid and chromatin dsDNA by locating endonuclease-generated 3' termini. Dominant TREX1 mutants (D18N, D200N, D200H) retain intact DNA binding but have dysfunctional active-site chemistry; competition assays demonstrate that the dominant mutants block access of WT TREX1 to DNA 3' termini through metal-dependent ssDNA binding in catalytically inactive active sites. Residues Arg-174 and Lys-175 act with Arg-128 to facilitate dsDNA melting for ssDNA loading. |
In vitro exonuclease assays with plasmid and chromatin dsDNA, competition assays with dominant mutant and WT TREX1 proteins |
The Journal of biological chemistry |
High |
21808053
|
| 2011 |
TREX1 R114H is a common AGS mutation; the R114H/R114H homodimer has 23-fold reduced ssDNA exonuclease activity. Compound heterodimers R114H/D201ins and R114H/A124ins exhibit 10-fold higher activity than the R114H homodimer, because Arg-114 residues from D201ins and A124ins protomers contribute to catalysis in the opposing R114H protomer across the dimer interface. |
Recombinant preparation of homo- and heterodimers, ssDNA and dsDNA exonuclease activity assays |
The Journal of biological chemistry |
High |
21937424
|
| 2012 |
Trex1 regulates lysosomal biogenesis and activates a subset of interferon-stimulated genes (ISGs/antiviral genes) independently of type I interferon. This interferon-independent activation in Trex1-deficient cells requires STING, TBK1, IRF3, and IRF7. Trex1-deficient cells also have an expanded lysosomal compartment, altered subcellular localization of TFEB, and diminished mTORC1 activity. |
Trex1⁻/⁻ mouse cells, STING/TBK1/IRF3/IRF7 genetic epistasis, transcriptomic profiling, lysosomal compartment analysis |
Nature immunology |
High |
23160154
|
| 2013 |
TREX1 C-terminal region controls cellular localization through ubiquitination. A highly conserved sequence in the CTR is required for ubiquitination at multiple lysine residues through a non-canonical ubiquitin linkage. Ubiquilin 1 was identified by proteomics as a TREX1 CTR-interacting protein (confirmed in vitro and in vivo), and ubiquilin 1 localizes TREX1 to cytosolic punctate structures dependent on the TREX1 CTR and catalytic core lysines. Disease-causing catalytically competent TREX1 mutants show differential ubiquitination and altered ubiquilin 1 co-localization. |
Deletion construct transfection, mass spectrometry proteomics, co-immunoprecipitation, in vitro binding assay, cotransfection co-localization |
The Journal of biological chemistry |
High |
23979357
|
| 2013 |
Oxidized DNA containing 8-hydroxyguanosine (8-OHG) is resistant to TREX1-mediated degradation. This resistance potentiates cGAS/STING-dependent cytosolic immune recognition, as oxidative modifications reduce TREX1's ability to degrade the DNA. 8-OHG arises in pathogen DNA during lysosomal ROS exposure and in NET DNA during oxidative burst. |
In vitro TREX1 degradation assays with oxidized vs. unmodified DNA, cytosolic DNA sensing assays, cell-based immune activation experiments |
Immunity |
High |
23993650
|
| 2014 |
TREX1 deficiency triggers cell-autonomous innate immune activation that is completely dependent on cGAS. Knockout of cGAS in TREX1-deficient cells abrogates spontaneous induction of interferon-stimulated genes, placing cGAS upstream of the type I IFN response in TREX1-deficient settings. |
TREX1/cGAS double-knockout cells, ISG expression assays |
Journal of immunology |
High |
24813208
|
| 2014 |
TREX1 directly interacts with PARP1 via PARP1's N-terminal zinc finger domains. This interaction occurs after nuclear translocation of TREX1 in response to DNA damage. TREX1 may contribute to stabilization of PARP1 levels and its activity during the DNA damage response. |
Mass spectrometry, co-immunoprecipitation assays, in vivo overexpression, domain mapping |
The Journal of biological chemistry |
Medium |
25278026
|
| 2015 |
TREX1 is also an exoribonuclease that degrades single-stranded RNA but not double-stranded RNA. The AGS disease mutant TREX1-D200N is defective in RNA degradation. TREX1 activity is inhibited by stretches of pyrimidine residues; TREX1 is active on native tRNA substrates. The substrate-binding site is open enough to accommodate the 2'-OH of RNA. |
In vitro exoribonuclease assays with purified TREX1, kinetic measurements, mutant protein analysis, structural analysis of published crystal structures |
The Journal of biological chemistry |
High |
25855793
|
| 2015 |
Crystal structure of TREX1 D18N in complex with dsDNA reveals a novel DNA-unwinding mechanism where TREX1 uses specific residues to separate polynucleotide strands for ssDNA loading into the active site. TREX1 D18N has dysfunctional dsDNA-degrading activity. TREX1 D18N knock-in mice develop systemic lupus-like inflammation with autoantibodies to dsDNA and immune complex deposition, demonstrating that dysfunctional dsDNA degradation alone is sufficient to cause lupus-like disease. |
X-ray crystallography of TREX1 D18N-dsDNA complex, knock-in mouse model, immunohistochemistry, autoantibody assays |
Proceedings of the National Academy of Sciences |
High |
25848017
|
| 2015 |
TREX1 C terminus suppresses immune activation independently of nuclease activity by interacting with the ER oligosaccharyltransferase (OST) complex and stabilizing its catalytic integrity. C-terminal frameshift mutations (as in RVCL) dysregulate the OST complex leading to free glycan release from dolichol carriers and immune activation. OST inhibition with aclacinomycin corrects glycan and immune defects in TREX1 frameshift mutant cells and mice. |
Co-immunoprecipitation of TREX1 with OST complex, glycan analysis, TREX1 KO and frameshift knock-in mice, patient lymphoblasts, aclacinomycin pharmacological rescue |
Immunity |
High |
26320659
|
| 2015 |
cGAS is required for lethal autoimmune disease in Trex1⁻/⁻ mice. Trex1⁻/⁻ cGAS⁻/⁻ double knockout mice are completely protected from lethality, show dramatically reduced tissue inflammation, and fail to develop autoantibodies, placing cGAS as a key driver of Trex1-deficiency-associated autoimmune disease. |
Double-knockout mouse genetics, histopathology, survival analysis, autoantibody measurement |
Journal of immunology |
High |
26223655
|
| 2017 |
DNA exonuclease TREX1 is induced by radiation doses above 12–18 Gy in cancer cells and attenuates immunogenicity by degrading cytosolic double-stranded DNA that accumulates upon radiation. Cytosolic DNA stimulates IFN-β secretion via cGAS and STING activation. At doses that do not induce TREX1, repeated irradiation amplifies IFN-β production, drives BATF3-dependent DC recruitment and CD8⁺ T cell priming for abscopal tumor rejection. |
Radiation dose–response experiments in cancer cells, siRNA knockdown, cGAS/STING pathway reporter assays, mouse tumor models, T cell depletion experiments |
Nature communications |
High |
28598415
|
| 2017 |
TREX1 suppresses L1 retrotransposon activity through a nuclease-independent mechanism. TREX1 interacts with L1 ORF1p protein and alters its intracellular localization, triggering ORF1p depletion and reducing L1-mediated nicking of genomic DNA. AGS-associated TREX1 mutants competent for DNA exonuclease activity are deficient in inducing ORF1p depletion. |
Co-immunoprecipitation, immunofluorescence co-localization, L1 retrotransposition and genomic nicking assays, AGS mutant analysis |
Nucleic acids research |
Medium |
28334850
|
| 2017 |
During mitosis, TREX1 is predominantly phosphorylated at C-terminal Serine-261 by Cyclin B/CDK1, and dephosphorylated at mitotic exit likely by PP1/PP2-type phosphatases. Mitotic phosphorylation does not affect DNase activity but phosphomimetic mutations disrupt TREX1 interaction with OST subunit RPN1 and elevate a glyco-gene expression signature. Thus cell-cycle-dependent phosphorylation regulates TREX1's OST-interacting function. |
Mass spectrometry identification of phosphorylation site, CDK1 inhibition, phosphomimetic mutant co-immunoprecipitation with RPN1, RNA-seq of Trex1⁻/⁻ MEFs with WT or phospho-mutants |
Cell reports |
High |
28297665
|
| 2017 |
TREX1 transcription is induced by IFN-γ in primary macrophages via STAT1 binding to IFN-γ activation site (GAS) boxes in the Trex1 promoter, and c-Jun (but not c-Fos, JunB, or CREB) binding to an AP-1 box. This was confirmed using STAT1 KO macrophages and EMSA/ChIP assays. |
EMSA, ChIP, transient transfection reporter assays, STAT1 KO macrophages, promoter mutational analysis |
Journal of immunology |
High |
21239708
|
| 2018 |
Crystal structures of TREX1 complexed with various DNA substrates (L-shaped, Y-shaped DNA) reveal that the Leu24-Pro25-Ser26 cluster serves to cap the non-scissile 5'-end for precise removal of short 3'-overhangs or to wedge into dsDNA for further digestion along the duplex. Arg128 shows consistent interaction patterns with the non-scissile strand across all structures. TREX1 can degrade dsDNA to completion. |
X-ray crystallography of multiple TREX1-DNA complexes, in vitro biochemical dsDNA degradation assays |
PLoS biology |
High |
29734329
|
| 2018 |
Tumor-derived exosomes from irradiated cancer cells (RT-TEX) transfer dsDNA to dendritic cells and stimulate STING-dependent IFN-β production. The IFN-stimulatory dsDNA cargo of RT-TEX is regulated by TREX1 expression in the parent cancer cells, demonstrating that TREX1 controls the immunostimulatory DNA content packaged into exosomes. |
Exosome purification and characterization, TREX1 knockdown in cancer cells, DC stimulation assays, in vivo tumor vaccination experiments |
Cancer immunology research |
Medium |
29907693
|
| 2021 |
cGAS-DNA phase separation inhibits TREX1-mediated DNA degradation. cGAS phase separation forms a selective environment that suppresses TREX1 catalytic function and restricts DNA degradation to the droplet periphery. An AGS-associated TREX1 mutation increases TREX1 penetration into the repressive droplet interior, specifically impairing degradation of phase-separated DNA. |
In vitro phase separation reconstitution, TREX1 activity assays on phase-separated DNA, confocal imaging of droplets, disease mutant analysis |
Molecular cell |
High |
33606975
|
| 2021 |
The ER-associated nuclease TREX1 inhibits cGAS activation at micronuclei by degrading micronuclear DNA upon micronuclear envelope rupture. The ER accesses ruptured micronuclei enabling TREX1 nucleolytic attack. TREX1 mutations that cause immune disease untether TREX1 from the ER, disrupt localization to micronuclei, diminish micronuclear DNA damage, and enhance cGAS activation. ER tethering is thus mechanistically required for TREX1's role in preventing innate immune activation at micronuclei. |
Micronuclei purification, TREX1 localization by immunofluorescence, ER membrane tracking, disease mutant analysis, cGAS activation assays, functional nuclease activity at micronuclei |
Molecular cell |
High |
33476576
|
| 2021 |
TREX1 translocates into the nucleus after nuclear envelope rupture and is required to induce DNA damage in this context. Inside the mammary duct, cellular crowding leads to nuclear envelope ruptures that generate TREX1-dependent DNA damage, driving progression of in situ carcinoma to the invasive stage. |
Live-cell imaging, TREX1 nuclear translocation assays after NE rupture, TREX1 KO/knockdown, in vivo mammary duct compression models, DNA damage markers |
Cell |
High |
34551315
|
| 2022 |
Crystal structures of human TREX1 in apo (1.25 Å) and DNA-bound (2.2 Å) conformations establish complete solvation of the exonuclease active site and identify specific substitutions involved in DNA recognition. Mapping of all human disease-associated mutations identifies distinct categories affecting enzymatic function, protein stability, and interaction with cGAS-DNA liquid droplets. |
X-ray crystallography at 1.25 Å (apo) and 2.2 Å (DNA complex), comprehensive mutation mapping |
Nature communications |
High |
35879334
|
| 2022 |
TREX1 degrades the 3' end of the small excised damage-containing DNA oligonucleotides (~30 nt, sedDNA) produced by nucleotide excision repair. TREX1 knockdown increases sedDNA levels and their association with NER proteins TFIIH and RPA; overexpression of WT but not nuclease-inactive TREX1 diminishes sedDNA levels. Purified TREX1 efficiently degrades DNA 3' of UV photoproducts in sedDNA. TREX1 modulation does not affect NER efficiency or cell survival. |
RNAi screen, TREX1 knockdown/overexpression in UV-irradiated cells, in vitro assays with purified TREX1 and synthetic sedDNA substrates |
Nucleic acids research |
High |
35357486
|
| 2022 |
Purified human TREX1 repairs 3'-PUA-peptide/protein DNA-protein cross-links (DPCs) arising from abasic sites, acting as an exonuclease on the 3'-PUA-modified terminus. TREX1 can directly repair 3'-PUA-histone DPCs but not 3'-PUA-PARP1 DPCs unless proteolysis occurs first. Kinetic constants were determined for DPC repair by TREX1. |
In vitro enzymatic assays with purified recombinant TREX1 and synthetic 3'-PUA-peptide adducts, kinetic analysis, histone and PARP1 DPC substrates |
Nucleic acids research |
High |
35349719
|
| 2023 |
TREX1 can digest ssRNA and DNA/RNA hybrids but not dsRNA. Crystal structures of TREX1-RNA product and TREX1-nucleotide complexes show 2'-OH does not impose steric hindrance for RNA recognition. MD simulations and binding affinity measurements with synthetic DNA-RNA junctions demonstrate that 2'-OH-mediated intra-chain hydrogen bonding in RNA increases conformational rigidity, reducing TREX1 binding affinity and catalytic cleavage efficiency. |
In vitro exonuclease activity assays, X-ray crystallography, all-atom molecular dynamics simulations, binding affinity measurements |
Nucleic acids research |
High |
37870446
|
| 2023 |
TREX1 degrades cytoplasmic mitochondrial DNA (mtDNA) released during influenza virus infection, preventing cGAS/STING-mediated antiviral sensing. Infection triggers release of mtDNA into the cytoplasm; TREX1 metabolizes this self-DNA, thereby preventing amplification of antiviral signaling and thus aiding viral replication. |
CRISPR-based genome-wide fitness screen during influenza infection, TREX1 KO cells, mtDNA accumulation assays, cGAS/STING pathway reporters |
Cell host & microbe |
High |
37652009
|
| 2024 |
TREX1 expression is coordinately induced with STING by autocrine IFN and downstream STAT1 in cancer cells, acting as a negative feedback mechanism. TREX1 restrains STING-dependent nucleic acid sensing via its catalytic DNA-degrading function. TREX1 inactivation in cancer cells unleashes STING-IFN signaling, recruiting T cells and NK cells and cooperating with PD-1 blockade. |
Cancer cell TREX1 KO/knockdown, STING pathway reporter assays, in vivo mouse tumor models with immune cell depletion, RNA-seq, combination immunotherapy experiments |
Cancer discovery |
High |
38227896
|
| 2024 |
TREX1 C-terminal frameshift variants associated with RVCL mislocalize to the nucleus (due to deletion of the ER-anchoring domain) and inhibit homology-directed repair (HDR), causing DNA deletions. RVCL TREX1 mutants increase cellular vulnerability to DNA damage induced by chemotherapy and cytokines, and cells expressing these mutants are depleted in vivo. Mechanistic studies in Drosophila, mice, and human cells confirm nuclear TREX1 causes DNA damage and disrupts HDR. |
RVCL patient cell analysis, mouse models, Drosophila genetics, CRISPR HDR assays, DNA damage marker analysis, PARP inhibitor sensitivity assays |
Nature communications |
High |
38824133
|
| 2024 |
TREX1 degrades single-stranded and linearized double-stranded DNA repair templates used for CRISPR-Cas9-mediated HDR, reducing HDR efficiency. TREX1 expression level serves as a biomarker for HDR efficiency across cell types. TREX1 knockout or use of chemically protected ssDNA templates rescues HDR efficiency by 2- to 8-fold in TREX1-expressing cells including primary T cells and hematopoietic stem/progenitor cells. |
Genome-wide CRISPR screen for HDR suppressors in Fanconi anemia lymphoblasts, TREX1 KO in multiple cell types, HDR efficiency assays with protected vs. unprotected templates |
Nature biotechnology |
High |
39134754
|
| 2014 |
Arg-62 residues of TREX1 extend across the dimer interface into the active site of the opposing protomer to coordinate substrate DNA and affect catalysis in trans. The TREX1(R62A/R62A) homodimer exhibits ~50-fold reduced ssDNA and dsDNA degradation. Dominant mutants (D18H, D18N, D200H, D200N) compound heterodimers with R62A in the opposing protomer show higher activity than the corresponding homodimers, demonstrating that Arg-62 provides structural elements required for full catalytic activity in the opposing protomer. |
Site-directed mutagenesis, recombinant homo- and heterodimer preparation, in vitro ssDNA and dsDNA exonuclease activity assays |
The Journal of biological chemistry |
High |
24616097
|