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Structures of mismatch replication errors observed in a DNA polymerase.
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.
Duke Scholars
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- Pyrimidines
- Purines
- Protein Structure, Tertiary
- Nucleotides
- Mutation
- Models, Molecular
- Geobacillus stearothermophilus
- Developmental Biology
- DNA-Directed DNA Polymerase
- DNA Replication
Citation
![Journal cover image](https://secure.syndetics.com/index.aspx?isbn=/lc.gif&issn=0092-8674&client=dukeuniv)
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Pyrimidines
- Purines
- Protein Structure, Tertiary
- Nucleotides
- Mutation
- Models, Molecular
- Geobacillus stearothermophilus
- Developmental Biology
- DNA-Directed DNA Polymerase
- DNA Replication