cd09857

PIN domain of Exonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs; Exonuclease-1 (EXO1) is involved in multiple, eukaryotic DNA metabolic pathways, including DNA replication processes (5' flap DNA endonuclease activity and double stranded DNA 5'-exonuclease activity), DNA repair processes (DNA mismatch repair (MMR) and post-replication repair (PRR)), recombination, and telomere integrity. EXO1 functions in the MMS2 error-free branch of the PRR pathway in the maintenance and repair of stalled replication forks. Studies also suggest that EXO1 plays both structural and catalytic roles during MMR-mediated mutation avoidance. EXO1 belongs to the FEN1-EXO1-like family of structure-specific, 5' nucleases. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region (I domain) of variable length (approximately 43 residues in EXO1 PIN domains) and a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included here) and the helical arch/clamp region are involved in DNA binding. Nucleases within this group also have a carboxylate-rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+/Mn2+). EXO1 nucleases also have C-terminal Mlh1- and Msh2-binding domains which allow interaction with MMR and PRR proteins, respectively.