Target intelligence / Profile preview

Exonuclease 5 (EXO5)

Target
EXO5
Molecular classification
Enzyme, Exonuclease, Endonuclease, DNA repair protein
01

Overview

Exonuclease 5 (EXO5) is an iron-sulfur cluster containing bidirectional exonuclease that loads onto single-stranded DNA ends, especially at stalled replication forks, and slides along the DNA, performing nucleolytic cleavage with a strong preference for the 5'-end. Its activity is regulated by replication protein A (RPA), which enforces 5'-directionality. EXO5 is involved in repairing DNA damage such as UV-induced lesions and interstrand cross-links, critical for genome stability. It acts in concert with the BLM helicase and ATR kinase, and its upregulation is associated with increased mutation load and poor prognosis in cancers. Sequence homologs in yeast are essential for mitochondrial genome maintenance, but mammalian EXO5 is nuclear and does not affect mitochondrial DNA[1][2][3][4].

Other names
Exonuclease 5EXO5Exonuclease VC1orf176DEM1hExo5Defects in morphology protein 1 homologprobable exonuclease VFLJ21144
02

Mechanism of action

Bidirectional exonuclease activity (primarily 5'-3' when regulated by RPA); repair of DNA lesions by processing single-stranded DNA ends; functional interaction with BLM helicase and ATR kinase for replication fork restart

03

Biological functions

DNA repairGenome stabilityDNA replication fork restartResponse to DNA damage
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Disease associations

Cancer (oncogenic potential if upregulated)Retinitis pigmentosa 13Combined oxidative phosphorylation deficiency 8
05

Safety considerations

Upregulation may increase genome instability and mutation burden in tumorsGenetic defects (depletion/loss) sensitize cells to DNA-damaging agents and cause chromosome abnormalities, including triradial chromosomes and unresolved replication forks
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Biomarkers

Elevated EXO5 expression may serve as a prognostic biomarker in tumors, correlating with poor patient survival and increased mutation load

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