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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]
Mutations in this gene may lead to Aicardi-Goutieres syndrome .
^ a b c GRCh38: Ensembl release 89: ENSG00000183479 – Ensembl , May 2017^ a b c 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 (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 . ^ a b "Entrez Gene: TREX2 three prime repair exonuclease 2" .^ Lung, Genesis (Nov 2021). "Precise Correction of A1AT E342K by Modified NGA PAM Prime Editing and Determination of Prime Editing Inhibition by TREX2" . ^ 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. ^ 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. ^ 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).
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Overview of all the structural information available in the PDB for UniProt : Q9BQ50 PDBe-KB .
Overview of all the structural information available in the PDB for UniProt : Q9R1A9 PDBe-KB .
