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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].
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
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