DEDDy 3'-5' exonuclease domain of WRN and similar proteins
WRN is a unique RecQ DNA helicase exhibiting an exonuclease activity. It contains a DEDDy-type DnaQ-like 3'-5' exonuclease domain possessing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific YX(3)D pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. Mutations in the WRN gene cause Werner syndrome, an autosomal recessive disorder associated with premature aging and increased susceptibility to cancer and type II diabetes. WRN interacts with key proteins involved in DNA replication, recombination, and repair. It is believed to maintain genomic stability and life span by participating in DNA processes. WRN is stimulated by Ku70/80, an important regulator of genomic stability.