Logo image
Back
Mechanism of Efficient and Accurate Nucleotide Incorporation Opposite 7,8-Dihydro-8-Oxoguanine by Saccharomyces cerevisiae DNA Polymerase η
Journal article   Peer reviewed

Mechanism of Efficient and Accurate Nucleotide Incorporation Opposite 7,8-Dihydro-8-Oxoguanine by Saccharomyces cerevisiae DNA Polymerase η

Karissa D Carlson and M. Todd Washington
Molecular and cellular biology, Vol.25(6), pp.2169-2176
03/2005
DOI: 10.1128/MCB.25.6.2169-2176.2005
PMCID: PMC1061627
PMID: 15743815
url
http://dx.doi.org/10.1128/MCB.25.6.2169-2176.2005View
Open Access

Abstract

Most DNA polymerases incorporate nucleotides opposite template 7,8-dihydro-8-oxoguanine (8-oxoG) lesions with reduced efficiency and accuracy. DNA polymerase (Pol) η, which catalyzes the error-free replication of template thymine-thymine (TT) dimers, has the unique ability to accurately and efficiently incorporate nucleotides opposite 8-oxoG templates. Here we have used pre-steady-state kinetics to examine the mechanisms of correct and incorrect nucleotide incorporation opposite G and 8-oxoG by Saccharomyces cerevisiae Pol η. We found that Pol η binds the incoming correct dCTP opposite both G and 8-oxoG with similar affinities, and it incorporates the correct nucleotide bound opposite both G and 8-oxoG with similar rates. While Pol η incorporates an incorrect A opposite 8-oxoG with lower efficiency than it incorporates a correct C, it does incorporate A more efficiently opposite 8-oxoG than opposite G. This is mainly due to greater binding affinity for the incorrect incoming dATP opposite 8-oxoG. Overall, these results show that Pol η replicates through 8-oxoG without any barriers introduced by the presence of the lesion.
 Chromosome Structure and Dynamics

Details

Metrics

13 Record Views
64 Times Cited - Web of Science
Logo image