InterPro domain: IPR044752

This is the PIN domain found in animal exonuclease-1 (EXO1) and its paralogue from yeasts, Din7. EXO1 is a 5'-3' exonuclease that functions in DNA mismatch repair (MMR), double-strand break repair, replication, recombination and telomere integrity [ 1 , 2 , 3 ]. It also possesses a flap-endonuclease activity [ 4 , 4 ], being a member of the Flap endonuclease-like (FEN-like) family, which are structure-specific endonucleases capable of cleaving single‐stranded DNA or RNA at the bifurcated end of a base‐paired duplex. DIN7 is involved in mitochondrial DNA repair and replication [ 5 ].

PIN domains belong to a large nuclease superfamily, which share a common core fold consisting of a three‐layered alpha/beta/alpha core motif with a central, parallel five‐stranded beta‐sheet. Its active site, possess invariant acidic amino acid residues and binds one or more divalent metal ions [ 6 , 7 ].

1. Reconstitution of 5'-directed human mismatch repair in a purified system. Cell 122, 693-705
2. Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA. Oncogene 23, 1457-68
3. Characterization of nuclease-dependent functions of Exo1p in Saccharomyces cerevisiae. DNA Repair (Amst.) 1, 895-912
4. The RAD2 domain of human exonuclease 1 exhibits 5' to 3' exonuclease and flap structure-specific endonuclease activities. J. Biol. Chem. 274, 37763-9
5. Enhanced expression of the DNA damage-inducible gene DIN7 results in increased mutagenesis of mitochondrial DNA in Saccharomyces cerevisiae. Mol. Genet. Genomics 269, 632-9
6. Comprehensive classification of the PIN domain-like superfamily. Nucleic Acids Res. 45, 6995-7020
7. Structural conservation of the PIN domain active site across all domains of life. Protein Sci. 26, 1474-1492