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Description

Exonuclease 1 (UniProt: Q9UQ84, also known as hExo1, Exonuclease I, hExoI) is encoded by the EXO1 (also known as EXOI, HEX1) gene (Gene ID: 9156) in human. Exonuclease 1 is a magnesium-dependent protein with 5&prime, to 3&prime, exonuclease and an RNase H activity. It may also possess a cryptic 3&prime,?5&prime, double-stranded DNA exonuclease activity. It is highly expressed in bone marrow, testis and thymus. Higher levels of expression are also observed in fetal liver. Lower expression has been observed in colon, lymph nodes, ovary, placenta, prostate, small intestine, spleen, and stomach. It functions in DNA mismatch repair to excise mismatch-containing DNA tracts directed by strand breaks located either 5&prime, or 3&prime, to the mismatch. It interacts physically with the DNA mismatch repair proteins, Msh2 and Mlh1, and is involved in the excision of the mispaired nucleotide. Exonuclease 1 is phosphorylated upon DNA damage and in response to agents stalling DNA replication, probably by ATM or ATR. It is shown to be phosphorylated at Serine 454, Threonine 621, and Serine 714 upon DNA-damage caused by treatment with hydroxyurea, but not upon IR treatment. The hydroxyurea-induced triple phosphorylation of exonuclease 1 facilitates destabilization/degradation of the protein.