Biology:TREX2
From HandWiki
Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Three prime repair exonuclease 2 is an enzyme that in humans is encoded by the TREX2 gene.[1][2]
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.[2]
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,[3] and replicated by Koeppel et al. in 2023.[4] 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.[5][6]
Mutations in this gene may lead to Aicardi-Goutieres syndrome.
References
- ↑ "Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'-->5' exonucleases". J Biol Chem 274 (28): 19655–60. Aug 1999. doi:10.1074/jbc.274.28.19655. PMID 10391904.
- ↑ 2.0 2.1 "Entrez Gene: TREX2 three prime repair exonuclease 2". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=11219.
- ↑ Lung, Genesis (Nov 2021). "Precise Correction of A1AT E342K by Modified NGA PAM Prime Editing and Determination of Prime Editing Inhibition by TREX2". https://dash.harvard.edu/handle/1/37370046.
- ↑ Koeppel, Jonas; Weller, Juliane; Peets, Elin Madli; Pallaseni, Ananth; Kuzmin, Ivan; Raudvere, Uku; Peterson, Hedi; Liberante, Fabio Giuseppe et al. (2023). "Prediction of prime editing insertion efficiencies using sequence features and DNA repair determinants". Nature Biotechnology 41 (10): 1444–1456. doi:10.1038/s41587-023-01678-y. PMID 36797492.
- ↑ Yin, Jianhang; Lu, Rusen; Xin, Changchang; Wang, Yuhong; Ling, Xinyu; Li, Dong; Zhang, Weiwei; Liu, Mengzhu et al. (Mar 2022). "Cas9 exo-endonuclease eliminates chromosomal translocations during genome editing". Nature Communications 13 (1): 1204. doi:10.1038/s41467-022-28900-w. PMID 35260581. Bibcode: 2022NatCo..13.1204Y.
- ↑ 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). https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(23)00290-1.
Further reading
- "The 3' 5' exonucleases". Nat. Rev. Mol. Cell Biol. 3 (5): 364–76. 2002. doi:10.1038/nrm804. PMID 11988770.
- "Expressed STSs and transcription of human Xq28". Gene 187 (2): 185–91. 1997. doi:10.1016/S0378-1119(96)00772-X. PMID 9099879.
- "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. 2001. doi:10.1101/gr.143000. PMID 11076863.
- "Identification of two proteins, S14 and UIP1, that interact with UCH37". FEBS Lett. 488 (3): 201–5. 2001. doi:10.1016/S0014-5793(00)02436-4. PMID 11163772. Bibcode: 2001FEBSL.488..201L.
- "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. 2001. doi:10.1093/embo-reports/kvd058. PMID 11256614.
- "Structure and expression of the TREX1 and TREX2 3' --> 5' exonuclease genes". J. Biol. Chem. 276 (18): 14718–27. 2001. doi:10.1074/jbc.M010051200. PMID 11278605.
- "Excision of 3' termini by the Trex1 and TREX2 3'-->5' exonucleases. Characterization of the recombinant proteins". J. Biol. Chem. 276 (20): 17022–9. 2001. doi:10.1074/jbc.M100623200. PMID 11279105.
- "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "[The correcting role of autonomous 3'-->5' exonucleases in mammalian multienzyme DNA polymerase complexes]". Mol. Biol. (Mosk.) 36 (6): 1055–61. 2003. PMID 12500544.
- "The TREX2 3'-->5' exonuclease physically interacts with DNA polymerase delta and increases its accuracy". ScientificWorldJournal 2: 275–81. 2004. doi:10.1100/tsw.2002.99. PMID 12806015.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. 2004. doi:10.1101/gr.2576704. PMID 15489336.
- "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. 2005. doi:10.1016/j.advenzreg.2003.11.010. PMID 15581481.
- "The human TREX2 3' -> 5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis". J. Biol. Chem. 280 (15): 15212–8. 2005. doi:10.1074/jbc.M500108200. PMID 15661738.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. 2006. doi:10.1093/nar/gkj139. PMID 16381901.
- "Human-specific nonsense mutations identified by genome sequence comparisons". Hum. Genet. 119 (1–2): 169–78. 2007. doi:10.1007/s00439-005-0125-6. PMID 16395595. https://zenodo.org/record/1232721.
- "Biochemical and cellular characteristics of the 3' -> 5' exonuclease TREX2". Nucleic Acids Res. 35 (8): 2682–94. 2007. doi:10.1093/nar/gkm151. PMID 17426129.
- "Increased Susceptibility to Skin Carcinogenesis in TREX2 Knockout Mice". Cancer Research 69 (16): 6676–84. 2009. 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.
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