A general structure for DNA-dependent DNA polymerases.
In addition to the general 3'-5' exonuclease domain described by Bernad et al. [Cell 59 (1989) 219-228] significant amino acid (aa) sequence similarity has been found in the C-terminal portion of 27 DNA-dependent DNA polymerases belonging to the two main superfamilies: (i) Escherichia coli DNA polymerase I (PolI)-like prokaryotic DNA polymerases, and (ii) DNA polymerase alpha-like prokaryotic and eukaryotic (viral and cellular) DNA polymerases. The six most conserved C-terminal regions, spanning approx. 340 aa, are located in the same linear arrangement and contain highly conserved motifs and critical residues involved in the polymerization function. According to the three-dimensional model of PolIk (Klenow fragment), these six conserved regions are located in the proposed polymerization domain, forming the metal and dNTP binding sites and the cleft for holding the DNA template. Site-directed mutagenesis in the phi 29 DNA polymerase supports some of these structural predictions. Therefore, it is likely that a 'Klenow-like core', containing the DNA polymerase and 3'-5' exonuclease activities, has evolved from a common ancestor, giving rise to the present-day prokaryotic and eukaryotic DNA polymerases.
Blanco
L
L
Centro de Biología Molecular (CSIC-UAM), Universidad Autónoma, Madrid, Spain.
Bernad
A
A
Blasco
M A
MA
Salas
M
M
D000595:Amino Acid Sequence; D000818:Animals; D004256:DNA Polymerase I / Q000235:genetics; D004257:DNA Polymerase II / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004926:Escherichia coli / Q000201:enzymology; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D014780:Viruses / Q000235:genetics
D004256:DNA Polymerase I; D004257:DNA Polymerase II; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; D043211:Exodeoxyribonuclease V