Structures of mismatch replication errors observed in a DNA polymerase.

Published

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 2004

Published In

Volume / Issue

  • 116 / 6

Start / End Page

  • 803 - 816

PubMed ID

  • 15035983

Pubmed Central ID

  • 15035983

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/s0092-8674(04)00252-1

Language

  • eng