ARE THERE HIGHLY CONSERVED DNA-POLYMERASE 3'-]5' EXONUCLEASE MOTIFS

It was proposed by Bernad et al. [Cell 59 (1989) 219-228] and Blanco e t al. [Gene 100 (1991) 27-38] that the 3' --> 5' exonuclease (Exo) dom ain of Escherichia coli DNA polymerase I (PolI) is structurally and fu nctionally conserved among prokaryotic and eukaryotic DNA polymerases. The basis for this claim is the presence of three short peptide seque nces in many DNA polymerases that resemble PolI sequences that have be en shown by x-ray crystallographic and genetic engineering studies to be metal ion binding sites that are essential for PolI 3' --> 5' Exo a ctivity [Derbyshire et al., Science 240 (1988) 199-201]. This claim is made even though there is little amino acid (aa) sequence similarity between PolI and many eukaryotic and viral DNA polymerases and in spit e of significant differences in the amount of 3' --> 5' Exo activity i n the DNA polymerases compared. For at least one DNA polymerase, bacte riophage T4 DNA polymerase, one of the proposed conserved Exo sequence s does not appear to he important for 3' --> 5' Exo activity. This T4 DNA polymerase result provides a reminder that caution must be used wh en weak aa sequence similarities are used to predict protein structure and function.