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Science 24 June 1994:
Vol. 264. no. 5167, pp. 1930 - 1935
DOI: 10.1126/science.7516581
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Articles

Science, Vol 264, Issue 5167, 1930-1935
Copyright © 1994 by American Association for the Advancement of Science

articles

Crystal structure of rat DNA polymerase beta: evidence for a common polymerase mechanism

MR Sawaya, H Pelletier, A Kumar, SH Wilson, and J Kraut

Department of Chemistry, University of California, San Diego 92093-0317.

Structures of the 31-kilodalton catalytic domain of rat DNA polymerase beta (pol beta) and the whole 39-kilodalton enzyme were determined at 2.3 and 3.6 angstrom resolution, respectively. The 31-kilodalton domain is composed of fingers, palm, and thumb subdomains arranged to form a DNA binding channel reminiscent of the polymerase domains of the Klenow fragment of Escherichia coli DNA polymerase I, HIV-1 reverse transcriptase, and bacteriophage T7 RNA polymerase. The amino-terminal 8-kilodalton domain is attached to the fingers subdomain by a flexible hinge. The two invariant aspartates found in all polymerase sequences and implicated in catalytic activity have the same geometric arrangement within structurally similar but topologically distinct palms, indicating that the polymerases have maintained, or possibly re-evolved, a common nucleotidyl transfer mechanism. The location of Mn2+ and deoxyadenosine triphosphate in pol beta confirms the role of the invariant aspartates in metal ion and deoxynucleoside triphosphate binding.


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dNTP Binding to HIV-1 Reverse Transcriptase and Mammalian DNA Polymerase beta as Revealed by Affinity Labeling with a Photoreactive dNTP Analog.
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In Vitro Bypass Replication of the Cisplatin-d(GpG) Lesion by Calf Thymus DNA Polymerase beta and Human Immunodeficiency Virus Type I Reverse Transcriptase Is Highly Mutagenic.
J.-S. Hoffmann, M.-J. Pillaire, D. Garcia-Estefania, S. Lapalu, and G. Villani (1996)
J. Biol. Chem. 271, 15386-15392
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Enzyme-DNA Interactions Required for Efficient Nucleotide Incorporation and Discrimination in Human DNA Polymerase beta.
W. A. Beard, W. P. Osheroff, R. Prasad, M. R. Sawaya, M. Jaju, T. G. Wood, J. Kraut, T. A. Kunkel, and S. H. Wilson (1996)
J. Biol. Chem. 271, 12141-12144
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Excision of deoxyribose phosphate residues by DNA polymerase beta during DNA repair.
Y Matsumoto and K Kim (1995)
Science 269, 699-702
   Abstract »    PDF »
Crystal structure of DCoH, a bifunctional, protein-binding transcriptional coactivator.
J. Endrizzi, J. Cronk, W Wang, G. Crabtree, and T Alber (1995)
Science 268, 556-559
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A DNA Polymerase beta in the Mitochondrion of the Trypanosomatid Crithidia fasciculata.
A. F. Torri and P. T. Englund (1995)
J. Biol. Chem. 270, 3495-3497
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Active Site Mapping of the Catalytic Mouse Primase Subunit by Alanine Scanning Mutagenesis.
W. C. Copeland and X. Tan (1995)
J. Biol. Chem. 270, 3905-3913
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Deoxynucleoside Triphosphate and Pyrophosphate Binding Sites in the Catalytically Competent Ternary Complex for the Polymerase Reaction Catalyzed by DNA Polymerase I (Klenow Fragment).
M. Astatke, N. D. F. Grindley, and C. M. Joyce (1995)
J. Biol. Chem. 270, 1945-1954
   Abstract »    Full Text »    PDF »
Footprint analysis of replicating murine leukemia virus reverse transcriptase.
B. Wohrl, M. Georgiadis, A Telesnitsky, W. Hendrickson, and S. Le Grice (1995)
Science 267, 96-99
   Abstract »    PDF »
Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases.
F Dyda, A. Hickman, T. Jenkins, A Engelman, R Craigie, and D. Davies (1994)
Science 266, 1981-1986
   Abstract »    PDF »
A unified polymerase mechanism for nonhomologous DNA and RNA polymerases.
T. Steitz, S. Smerdon, J Jager, and C. Joyce (1994)
Science 266, 2022-2025
   PDF »
Polymerase structures and mechanism.
H Pelletier (1994)
Science 266, 2025-2026
   PDF »
DNA Structure and Aspartate 276 Influence Nucleotide Binding to Human DNA Polymerase beta . IMPLICATION FOR THE IDENTITY OF THE RATE-LIMITING CONFORMATIONAL CHANGE.
B. J. Vande Berg, W. A. Beard, and S. H. Wilson (2001)
J. Biol. Chem. 276, 3408-3416
   Abstract »    Full Text »    PDF »
The Conserved Active Site Motif A of Escherichia coli DNA Polymerase I Is Highly Mutable.
A. Shinkai, P. H. Patel, and L. A. Loeb (2001)
J. Biol. Chem. 276, 18836-18842
   Abstract »    Full Text »    PDF »
Terminal Deoxynucleotidyl Transferase Indiscriminately Incorporates Ribonucleotides and Deoxyribonucleotides.
J.-B. Boule, F. Rougeon, and C. Papanicolaou (2001)
J. Biol. Chem. 276, 31388-31393
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)