TREX2

TREX2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1Y97
Identifiers
Aliases	TREX2 , three prime repair exonuclease 2
External IDs	OMIM: 300370; MGI: 1346343; HomoloGene: 8046; GeneCards: TREX2; OMA:TREX2 - orthologs
Gene location (Human) Chr. X chromosome (human) [1] Band Xq28 Start 153,444,473 bp [1] End 153,470,587 bp [1]
Gene location (Mouse) Chr. X chromosome (mouse) [2] Band X|X A7.3 Start 72,477,311 bp [2] End 72,478,950 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of abdomen skin of leg ascending aorta Descending thoracic aorta right coronary artery tibial arteries granulocyte left coronary artery ectocervix spleen Top expressed in esophagus lip embryo embryo skin of external ear skin of abdomen submandibular gland skin of back stomach umbilical cord More reference expression data BioGPS n/a
Gene ontology Molecular function nuclease activity exodeoxyribonuclease III activity exonuclease activity hydrolase activity protein homodimerization activity magnesium ion binding 3'-5'-exodeoxyribonuclease activity metal ion binding nucleic acid binding 3'-5' exonuclease activity Cellular component nucleus Biological process DNA repair cellular response to DNA damage stimulus nucleic acid phosphodiester bond hydrolysis DNA metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 11219 24102 Ensembl ENSG00000183479 ENSMUSG00000031372 UniProt Q9BQ50 Q9R1A9 RefSeq (mRNA) NM_080701 NM_080699 NM_080700 NM_011907 RefSeq (protein) NP_542432 NP_036037 Location (UCSC) Chr X: 153.44 – 153.47 Mb Chr X: 72.48 – 72.48 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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] , and replicated by Koeppel et al. in 2023 ^[8] . Subsequently, 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]} .

Mutations in this gene may lead to Aicardi-Goutieres syndrome.

References

1. GRCh38: Ensembl release 89: ENSG00000183479 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031372 – Ensembl, 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. "Entrez Gene: TREX2 three prime repair exonuclease 2".
7. Lung, Genesis (Nov 2021). "Precise Correction of A1AT E342K by Modified NGA PAM Prime Editing and Determination of Prime Editing Inhibition by TREX2".
8. Koeppel, Jonas; Weller, Juliane; Peets, Elin Madli; Pallaseni, Ananth; Kuzmin, Ivan; Raudvere, Uku; Peterson, Hedi; Liberante, Fabio Giuseppe; Parts, Leopold (2023). "Prediction of prime editing insertion efficiencies using sequence features and DNA repair determinants". Nature Biotechnology. 41: 1444–1456.
9. Yin, Jianhang; Lu, Rusen; Xin, Changchang; Wang, Yuhong; Ling, Xinyu; Li, Dong; Zhang, Weiwei; Liu, Mengzhu; Xie, Wutao; Kong, Lingyun; Si, Wen; Wei, Ping; Xiao, Bingbing; Lee, Hsiang-Ying; Liu, Tao (Mar 2022). "Cas9 exo-endonuclease eliminates chromosomal translocations during genome editing". Nature Communications. 13: 1204.
10. Wang, Yue; Feng, Yi-Li; Liu, Qian; Liu, Si-Cheng; Huang, Zhi-Cheng (Dec 2023). "TREX2 enables efficient genome disruption mediated by paired CRISPR-Cas9 nickases that generate 3′-overhanging ends". Cell Molecular Therapy. 34 (102072).

Further reading

• Shevelev IV, Hübscher U (2002). "The 3' 5' exonucleases". Nat. Rev. Mol. Cell Biol. 3 (5): 364–76. doi:10.1038/nrm804. PMID   11988770. S2CID   31605786.
• Esposito T, Ciccodicola A, Flagiello L, et al. (1997). "Expressed STSs and transcription of human Xq28". Gene. 187 (2): 185–91. 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 Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• Li T, Duan W, Yang H, et al. (2001). "Identification of two proteins, S14 and UIP1, that interact with UCH37". FEBS Lett. 488 (3): 201–5. 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, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. 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". J. Biol. Chem. 276 (18): 14718–27. 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". J. Biol. Chem. 276 (20): 17022–9. doi: 10.1074/jbc.M100623200 . PMID   11279105.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Shevelev IV, Beliakova NV, Kravetskaia TP, Krutiakov VM (2003). "[The correcting role of autonomous 3'-->5' exonucleases in mammalian multienzyme DNA polymerase complexes]". Mol. Biol. (Mosk.). 36 (6): 1055–61. PMID   12500544.
• Shevelev IV, Ramadan K, Hübscher U (2004). "The TREX2 3'-->5' exonuclease physically interacts with DNA polymerase delta and increases its accuracy". ScientificWorldJournal. 2: 275–81. doi: 10.1100/tsw.2002.99 . PMC   6009725 . PMID   12806015.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC   528930 . PMID   15489336.
• Perrino FW, Krol A, Harvey S, et al. (2005). "Sequence variants in the 3'-->5' deoxyribonuclease TREX2: identification in a genetic screen and effects on catalysis by the recombinant proteins". Adv. Enzyme Regul. 44: 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". J. Biol. Chem. 280 (15): 15212–8. doi: 10.1074/jbc.M500108200 . PMID   15661738.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
• Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 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". Hum. Genet. 119 (1–2): 169–78. 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 Res. 35 (8): 2682–94. doi:10.1093/nar/gkm151. PMC   1885668 . PMID   17426129.
• Parra D, Manils J, Castellana B, Viña-Vilaseca A, Morán-Salvador E, Vázquez-Villoldo N, Tarancón G, Borràs M, Sancho S, Benito C, Ortega S, and Soler C (2009). "Increased Susceptibility to Skin Carcinogenesis in TREX2 Knockout Mice". Cancer Research. 69 (16): 6676–84. doi: 10.1158/0008-5472.CAN-09-1208 . PMID   19654293.

External links

• 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 .