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TREX2

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TREX2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTREX2, three prime repair exonuclease 2
External IDsOMIM: 300370; MGI: 1346343; HomoloGene: 8046; GeneCards: TREX2; OMA:TREX2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_080701
NM_080699
NM_080700

NM_011907

RefSeq (protein)

NP_542432

NP_036037

Location (UCSC)Chr X: 153.44 – 153.47 MbChr X: 72.48 – 72.48 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000183479Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031372Ensembl, 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. ^ a b "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

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[edit]
  • 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.