Steady-state and pre-steady-state kinetic analysis of 8-oxo-7,8-dihydroguanosine triphosphate incorporation and extension by replicative and repair DNA polymerases.

  title={Steady-state and pre-steady-state kinetic analysis of 8-oxo-7,8-dihydroguanosine triphosphate incorporation and extension by replicative and repair DNA polymerases.},
  author={Heidi J. Einolf and Nathalie Schnetz-Boutaud and F. Peter Guengerich},
  volume={37 38},
The kinetics of 8-oxo-7,8-dihydroguanosine triphosphate (8-oxo-dGTP) incorporation into DNA by Escherichia coli polymerases I exo- (KF-) and II exo- (Pol II-), HIV-1 RT reverse transcriptase (HIV-1 RT), and bacteriophage T7 exo- (T7(-)) were examined to determine the misincorporation potential for 8-oxo-dGTP and to investigate the role of base pairing symmetry in DNA polymerase fidelity. 8-Oxo-dGTP was found to be a poor substrate for the four polymerases, with insertion efficiencies >10(4… 
Fidelity of Nucleotide Insertion at 8-Oxo-7,8-dihydroguanine by Mammalian DNA Polymerase δ
The presence of PCNA was found to be a more essential factor forucleotide incorporation opposite 8-oxoG adducts than unmodified DNA, increased pre-steady-state rates of nucleotide incorporation by >2 orders of magnitude, and was essential for nucleotide extension beyond 8-OxoG.
Single-turnover Kinetic Analysis of the Mutagenic Potential of 8-Oxo-7,8-dihydro-2′-deoxyguanosine during Gap-filling Synthesis Catalyzed by Human DNA Polymerases λ and β
DNA polymerase λ is more efficient than DNA polymerase β to fill this oxidized single-nucleotide gap, and the erroneous nucleotide incorporations catalyzed by DNA polymerases λ and β as well as the subsequent ligation catalyzed during base excision repair are a threat to genomic integrity.
Incorporation and Replication of 8-Oxo-deoxyguanosine by the Human Mitochondrial DNA Polymerase*
To assess the role of oxidative stress on the replication of mitochondrial DNA, we examined the kinetics of incorporation of 8-oxo-7,8-dihydroguanosine (8-oxodG) triphosphate catalyzed by the human
Efficient and High Fidelity Incorporation of dCTP Opposite 7,8-Dihydro-8-oxodeoxyguanosine by Sulfolobus solfataricus DNA Polymerase Dpo4*
DNA polymerases insert dATP opposite the oxidative damage product 7,8-dihydro-8-oxodeoxyguanosine ( 8-oxoG) instead of dCTP, to the extent of >90% with some polymerases, consistent with the low frequency of this frameshift event observed in the catalytic assays.
Nucleotide binding interactions modulate dNTP selectivity and facilitate 8-oxo-dGTP incorporation by DNA polymerase lambda
Low resolution crystal structures showing how Pol λ accommodates 8-oxo-dGTP in its active site indicate that when mispaired with dA, the oxidized nucleotide assumes the mutagenic syn-conformation, and is stabilized by multiple interactions.
Effects of 8-halo-7-deaza-2'-deoxyguanosine triphosphate on DNA synthesis by DNA polymerases and cell proliferation.
Results indicate that strong hydrogen bonding between 7-NH in the 8-oxo-G nucleobase and 1-N in the adenine at the active site of the DNA polymerase is required for the mutagenic effects.
The anti/syn conformation of 8-oxo-7,8-dihydro-2'-deoxyguanosine is modulated by Bacillus subtilis PolX active site residues His255 and Asn263. Efficient processing of damaged 3'-ends.
It is shown that, unlike most DNA polymerases, PolXBs exhibits a similar efficiency to stabilize the anti and syn conformation of 8oxodGTP at the catalytic site, and at least two conserved residues of the nucleotide binding pocket play opposite roles in the anti/syn conformation selectivity.
The base substitution fidelity of HIV-1 reverse transcriptase on DNA and RNA templates probed with 8-oxo-deoxyguanosine triphosphate.
The similarities in error rates and distribution indicate that, despite differences in the structures of free RNA x DNA and DNA x DNA duplexes, the polymerase active site that assembles upon substrate binding establishes a similar degree of nucleotide selectivity with both types of template-primers.
Cellular 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase activity of human and mouse MTH1 proteins does not depend on the proliferation rate.
It is concluded that the MTH1 expression manifested as the 8-oxo-dGTPase activity of its protein products in mammalian cells is not associated with proliferation rate, and this results will help in further testing of the hypothesis that M TH1 overexpression may be a specific marker of carcinogenesis and/or oxidative stress.
Kinetic basis for the differing response to an oxidative lesion by a replicative and a lesion bypass DNA polymerase from Sulfolobus solfataricus.
A kinetic basis is provided for a potential polymerase switching mechanism during 8-oxoG bypass whereby Dpo4 can switch with the stalled PolB1 at the replication fork to bypass and extend the damaged DNA and then switch off of the DNA substrate to allow continued replication of undamaged DNA by the more faithful PolB 1.