1NJY

THYMINE-THYMINE MISMATCH AT THE POLYMERASE ACTIVE SITE

Summary for 1NJY

• Entry DOI: 10.2210/pdb1njy/pdb
• Related: 1NJW 1NJX 1NJZ 1NK0 1NK4 1NK5 1NK6 1NK7 1NK8 1NK9 1NKB 1NKC 1NKE
• Related PRD ID: PRD_900003
• Descriptor: DNA PRIMER STRAND, DNA TEMPLATE STRAND, DNA POLYMERASE I, ... (8 entities in total)
• Functional Keywords: dna polymerase i, dna replication, klenow fragment, protein-dna complex, dna mismatch, transferase-dna complex, transferase/dna
• Biological source: Geobacillus stearothermophilus
• Total number of polymer chains: 3
• Total formula weight: 75828.44

Authors

Johnson, S.J.,Beese, L.S. (deposition date: 2003-01-02, release date: 2004-03-30, Last modification date: 2023-08-16)

Primary citation

Johnson, S.J.,Beese, L.S.
Structures of mismatch replication errors observed in a DNA polymerase.
Cell(Cambridge,Mass.), 116:803-816, 2004

PubMed Abstract: 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.

PubMed: 15035983
DOI: 10.1016/S0092-8674(04)00252-1

Experimental method

X-RAY DIFFRACTION (2 Å)