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Protein-coding gene in the species Homo sapiens
Three prime repair exonuclease 2 is an enzyme that in humans is encoded by the TREX2 gene .[ 5] [ 6]
This gene encodes a protein with 3' exonuclease activity. Enzymes with this activity are involved in DNA replication , repair, and recombination. Similarity to an E. coli protein suggests that this enzyme may be a subunit of DNA polymerase III , which does not have intrinsic exonuclease activity.[ 6]
Newer research has determined that TREX2 is also involved in flap endonuclease activity, as detected in the context of inhibiting gene-editing nickases that generate an extension flap such as prime editors that do not usually create a double-stranded break. This function was first demonstrated in a thesis by Lung in 2021,[ 7] [ 8] TREX2 has become incorporated into fusion enzymes for genetic engineering by multiple research groups for the purposes of reducing off-target edits which include chromosomal translocations and mismatched insertions.[ 9] [ 10]
1 2 3 GRCh38: Ensembl release 89: ENSG00000183479 – Ensembl , May 20171 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031372 – Ensembl , May 2017↑ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .↑ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .↑ Mazur DJ, Perrino FW (August 1999). "Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'-->5' exonucleases" . The Journal of Biological Chemistry . 274 (28): 19655– 19660. doi :10.1074/jbc.274.28.19655 PMID 10391904 . 1 2 "Entrez Gene: TREX2 three prime repair exonuclease 2" .↑ Lung G (November 2021). "Precise Correction of A1AT E342K by Modified NGA PAM Prime Editing and Determination of Prime Editing Inhibition by TREX2" . ↑ Koeppel J, Weller J, Peets EM, Pallaseni A, Kuzmin I, Raudvere U, et al. (October 2023). "Prediction of prime editing insertion efficiencies using sequence features and DNA repair determinants" . Nature Biotechnology . 41 (10): 1446– 1456. doi :10.1038/s41587-023-01678-y . PMC 10567557 PMID 36797492 . ↑ Yin J, Lu R, Xin C, Wang Y, Ling X, Li D, et al. (March 2022). "Cas9 exo-endonuclease eliminates chromosomal translocations during genome editing" . Nature Communications . 13 (1) 1204. Bibcode :2022NatCo..13.1204Y . doi :10.1038/s41467-022-28900-w PMC 8904484 PMID 35260581 . ↑ Wang Y, Feng YL, Liu Q, Xiao JJ, Liu SC, Huang ZC, et al. (December 2023). "TREX2 enables efficient genome disruption mediated by paired CRISPR-Cas9 nickases that generate 3'-overhanging ends" . Molecular Therapy. Nucleic Acids . 34 (102072) 102072. doi :10.1016/j.omtn.2023.102072 . PMC 10661556 PMID 38028195 .
Shevelev IV, Hübscher U (2002). "The 3' 5' exonucleases". Nature Reviews. Molecular Cell Biology . 3 (5): 364– 376. doi :10.1038/nrm804 . PMID 11988770 . S2CID 31605786 . Esposito T, Ciccodicola A, Flagiello L, Matarazzo MR, Migliaccio C, Cifarelli RA, et al. (March 1997). "Expressed STSs and transcription of human Xq28". Gene . 187 (2): 185– 191. doi :10.1016/S0378-1119(96)00772-X . PMID 9099879 . Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination" . Genome Research . 10 (11): 1788– 1795. doi :10.1101/gr.143000 . PMC 310948 PMID 11076863 . Li T, Duan W, Yang H, Lee MK, Bte Mustafa F, Lee BH, et al. (January 2001). "Identification of two proteins, S14 and UIP1, that interact with UCH37". FEBS Letters . 488 (3): 201– 205. Bibcode :2001FEBSL.488..201L . doi :10.1016/S0014-5793(00)02436-4 . hdl :10536/DRO/DU:30009147 PMID 11163772 . S2CID 40717095 . Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (September 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing" . EMBO Reports . 1 (3): 287– 292. doi :10.1093/embo-reports/kvd058 . PMC 1083732 PMID 11256614 . Mazur DJ, Perrino FW (2001). "Structure and expression of the TREX1 and TREX2 3' --> 5' exonuclease genes" . The Journal of Biological Chemistry . 276 (18): 14718– 14727. doi :10.1074/jbc.M010051200 PMID 11278605 . Mazur DJ, Perrino FW (2001). "Excision of 3' termini by the Trex1 and TREX2 3'-->5' exonucleases. Characterization of the recombinant proteins" . The Journal of Biological Chemistry . 276 (20): 17022– 17029. doi :10.1074/jbc.M100623200 PMID 11279105 . Shevelev IV, Beliakova NV, Kravetskaia TP, Krutiakov VM (2003). "[The correcting role of autonomous 3'-->5' exonucleases in mammalian multienzyme DNA polymerase complexes]". Molekuliarnaia Biologiia . 36 (6). Mosk: 1055– 1061. PMID 12500544 . Shevelev IV, Ramadan K, Hübscher U (2004). "The TREX2 3'-->5' exonuclease physically interacts with DNA polymerase delta and increases its accuracy" . TheScientificWorldJournal . 2 : 275– 281. doi :10.1100/tsw.2002.99 PMC 6009725 PMID 12806015 . Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline" . Genome Research . 14 (10B): 2136– 2144. doi :10.1101/gr.2576704 . PMC 528930 PMID 15489336 . Perrino FW, Krol A, Harvey S, Zheng SL, Horita DA, Hollis T, et al. (2004). "Sequence variants in the 3'-->5' deoxyribonuclease TREX2: identification in a genetic screen and effects on catalysis by the recombinant proteins". Advances in Enzyme Regulation . 44 (1): 37– 49. doi :10.1016/j.advenzreg.2003.11.010 . PMID 15581481 . Perrino FW, Harvey S, McMillin S, Hollis T (2005). "The human TREX2 3' -> 5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis" . The Journal of Biological Chemistry . 280 (15): 15212– 15218. doi :10.1074/jbc.M500108200 PMID 15661738 . Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . 437 (7062): 1173– 1178. Bibcode :2005Natur.437.1173R . doi :10.1038/nature04209 . PMID 16189514 . S2CID 4427026 . Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006" . Nucleic Acids Research . 34 (Database issue): D415–8. doi :10.1093/nar/gkj139 . PMC 1347501 PMID 16381901 . Hahn Y, Lee B (2007). "Human-specific nonsense mutations identified by genome sequence comparisons". Human Genetics . 119 (1– 2): 169– 178. doi :10.1007/s00439-005-0125-6 . PMID 16395595 . S2CID 21059468 . Chen MJ, Ma SM, Dumitrache LC, Hasty P (2007). "Biochemical and cellular characteristics of the 3' -> 5' exonuclease TREX2" . Nucleic Acids Research . 35 (8): 2682– 2694. doi :10.1093/nar/gkm151 . PMC 1885668 PMID 17426129 . Parra D, Manils J, Castellana B, Viña-Vilaseca A, Morán-Salvador E, Vázquez-Villoldo N, et al. (2009). "Increased Susceptibility to Skin Carcinogenesis in TREX2 Knockout Mice" . Cancer Research . 69 (16): 6676– 6684. doi :10.1158/0008-5472.CAN-09-1208 PMID 19654293 .
Overview of all the structural information available in the PDB for UniProt : Q9BQ50 (Human Three prime repair exonuclease 2) at the PDBe-KB . Overview of all the structural information available in the PDB for UniProt : Q9R1A9 (Mouse Three prime repair exonuclease 2) at the PDBe-KB .
