Journal
CELL
Volume 116, Issue 6, Pages 803-816Publisher
CELL PRESS
DOI: 10.1016/S0092-8674(04)00252-1
Keywords
-
Categories
Funding
- NCI NIH HHS [P01 CA92584] Funding Source: Medline
- NCRR NIH HHS [RR07707] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available