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PDBsum entry 2r8h
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Replication, transferase/DNA
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PDB id
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2r8h
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References listed in PDB file
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Key reference
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Title
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Insertion of dntps opposite the 1,N2-Propanodeoxyguanosine adduct by sulfolobus solfataricus p2 DNA polymerase IV.
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Authors
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Y.Wang,
S.K.Musser,
S.Saleh,
L.J.Marnett,
M.Egli,
M.P.Stone.
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Ref.
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Biochemistry, 2008,
47,
7322-7334.
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PubMed id
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Abstract
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1, N (2)-Propanodeoxyguanosine (PdG) is a stable structural analogue for the
3-(2'-deoxy-beta- d- erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3 H)-one
(M 1dG) adduct derived from exposure of DNA to base propenals and to
malondialdehyde. The structures of ternary polymerase-DNA-dNTP complexes for
three template-primer DNA sequences were determined, with the Y-family
Sulfolobus solfataricus DNA polymerase IV (Dpo4), at resolutions between 2.4 and
2.7 A. Three template 18-mer-primer 13-mer sequences,
5'-d(TCACXAAATCCTTCCCCC)-3'.5'-d(GGGGGAAGGATTT)-3' (template I),
5'-d(TCACXGAATCCTTCCCCC)-3'.5'-d(GGGGGAAGGATTC)-3' (template II), and
5'-d(TCATXGAATCCTTCCCCC)-3'.5'-d(GGGGGAAGGATTC)-3' (template III), where X is
PdG, were analyzed. With templates I and II, diffracting ternary complexes
including dGTP were obtained. The dGTP did not pair with PdG, but instead with
the 5'-neighboring template dC, utilizing Watson-Crick geometry. Replication
bypass experiments with the template-primer
5'-TCACXAAATCCTTACGAGCATCGCCCCC-3'.5'-GGGGGCGATGCTCGTAAGGATTT-3', where X is
PdG, which includes PdG in the 5'-CXA-3' template sequence as in template I,
showed that the Dpo4 polymerase inserted dGTP and dATP when challenged by the
PdG adduct. For template III, in which the template sequence was 5'-TXG-3', a
diffracting ternary complex including dATP was obtained. The dATP did not pair
with PdG, but instead with the 5'-neighboring T, utilizing Watson-Crick
geometry. Thus, all three ternary complexes were of the "type II" structure
described for ternary complexes with native DNA [Ling, H., Boudsocq, F.,
Woodgate, R., and Yang, W. (2001) Cell 107, 91-102]. The PdG adduct remained in
the anti conformation about the glycosyl bond in each of these threee ternary
complexes. These results provide insight into how -1 frameshift mutations might
be generated for the PdG adduct, a structural model for the exocylic M 1dG
adduct formed by malondialdehyde.
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