This domain is responsible for the 3'-5' exonuclease proofreading activity of E. coli DNA polymerase I (polI) and other enzymes, it catalyzes the hydrolysis of unpaired or mismatched nucleotides. This domain consists of the amino-terminal half of the Klenow fragment in E. coli polI it is also found in the Werner syndrome helicase (WRN), focus forming activity 1 protein (FFA-1) and ribonuclease D (RNase D). Werner syndrome is a human genetic disorder causing premature aging; the WRN protein has helicase activity in the 3'-5' direction. The FFA-1 protein is required for formation of a replication foci and also has helicase activity; it is a homolog of the WRN protein. RNase D is a 3'-5' exonuclease involved in tRNA processing. Also found in this family is the autoantigen PM/Scl thought to be involved in polymyositis-scleroderma overlap syndrome.