Family A and family B DNA polymerases are structurally related: evolutionary implications.
In order to establish the evolutionary relationship between the family A and B DNA polymerases, we have closely compared the 3'-->5' exonuclease domains between the Klenow fragment of E.coli DNA polymerase I (a family A DNA polymerase) and the bacteriophage PRD1 DNA polymerase, the smallest member of the DNA polymerase family B. Although the PRD1 DNA polymerase has a smaller 3'-->5' exonuclease domain, its active sites appear to be very similar to those of the Klenow fragment. Site-directed mutagenesis studies revealed that the residues important for the 3'-->5' exonuclease activity, particularly metal binding ligands for the Klenow fragment, are all conserved in the PRD1 DNA polymerase as well. The metal binding ligands are also essential for the strand-displacement activity of the PRD1 DNA polymerase. Based on these results and the studies by others in various systems, we conclude that family A and B DNA polymerases, at least in the 3'-->5' exonuclease domain, are structurally as well as evolutionarily related.
Zhu
W
W
Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson 85724.
Ito
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D005075:Biological Evolution; D003090:Coliphages / Q000201:enzymology; D017124:Conserved Sequence; D004256:DNA Polymerase I / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology*; D004279:DNA, Viral / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D008670:Metals / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016415:Sequence Alignment
D004279:DNA, Viral; D008670:Metals; D004256:DNA Polymerase I; D004259:DNA-Directed DNA Polymerase