Structures of mismatch replication errors observed in a DNA polymerase.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Johnson, SJ; Beese, LS
Published Date
- March 19, 2004
Published In
Volume / Issue
- 116 / 6
Start / End Page
- 803 - 816
PubMed ID
- 15035983
International Standard Serial Number (ISSN)
- 0092-8674
Digital Object Identifier (DOI)
- 10.1016/s0092-8674(04)00252-1
Language
- eng
Conference Location
- United States