1nk0
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ADENINE-GUANINE MISMATCH AT THE POLYMERASE ACTIVE SITE
OverviewOverview
Accurate DNA replication is essential for genomic stability. One mechanism by which high-fidelity DNA polymerases maintain replication accuracy involves stalling of the polymerase in response to covalent incorporation of mismatched base pairs, thereby favoring subsequent mismatch excision. Some polymerases retain a "short-term memory" of replication errors, responding to mismatches up to four base pairs in from the primer terminus. Here we a present a structural characterization of all 12 possible mismatches captured at the growing primer terminus in the active site of a polymerase. Our observations suggest four mechanisms that lead to mismatch-induced stalling of the polymerase. Furthermore, we have observed the effects of extending a mismatch up to six base pairs from the primer terminus and find that long-range distortions in the DNA transmit the presence of the mismatch back to the enzyme active site, suggesting the structural basis for the short-term memory of replication errors.
About this StructureAbout this Structure
1NK0 is a Protein complex structure of sequences from Geobacillus stearothermophilus with , and as ligands. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Full crystallographic information is available from OCA.
ReferenceReference
Structures of mismatch replication errors observed in a DNA polymerase., Johnson SJ, Beese LS, Cell. 2004 Mar 19;116(6):803-16. PMID:15035983
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