|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print November 22, 2005
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146
Corresponding Author: f.guengerich{at}vanderbilt.edu
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. Steady-state kinetics with the Y-family Sulfolobus solfataricus DNA polymerase IV (Dpo4) showed 25-fold higher incorporation efficiency of dCTP > dATP opposite 8-oxoG and 4-fold higher efficiency of extension beyond an 8-oxoG:C pair than an 8-oxoG:A pair. The catalytic efficiency for these events (with dCTP or C) was similar for G and 8-oxoG templates. Mass spectral analysis of extended DNA primers showed = 95% incorporation of dCTP > dATP opposite 8-oxoG. Pre-steady-state kinetics showed faster rates of dCTP incorporation opposite 8-oxoG than G. The measured Kd,dCTP was 15-fold lower for an oligonucleotide containing 8-oxoG than with G. Extension beyond an 8-oxoG:C pair was similar to G:C and faster than for an 8-oxoG:A pair, in contrast to other polymerases. The Ea for dCTP insertion opposite 8-oxoG was lower than opposite G. Crystal structures of Dpo4 complexes with oligonucleotides were solved with C, A, and G nucleoside triphosphates placed opposite 8-oxoG. With ddCTP, dCTP, and dATP the phosphodiester bonds were formed even in the presence of Ca2+. The 8-oxoG:C pair showed classic Watson-Crick geometry; the 8-oxoG:A pair was in the syn:anti configuration, with the A hybridized in a Hoogsteen pair with the 8-oxoG. With dGTP placed opposite 8-oxoG, pairing was not to the 8-oxoG but to the 5’ C (and in classic Watson-Crick geometry), consistent with the low frequency of this frameshift event observed in the catalytic assays.
J. Biol. Chem, 10.1074/jbc.M510889200
Submitted on October 5, 2005
Revised on November 16, 2005
Accepted on November 22, 2005
Efficient and high fidelity incorporation of dCTP opposite 7,8-dihydro-8-oxodeoxyguanosine by sulfolobus solfataricus DNA polymerase Dpo4
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. W. Beckman, Q. Wang, and F. P. Guengerich Kinetic Analysis of Correct Nucleotide Insertion by a Y-family DNA Polymerase Reveals Conformational Changes Both Prior to and following Phosphodiester Bond Formation as Detected by Tryptophan Fluorescence J. Biol. Chem., December 26, 2008; 283(52): 36711 - 36723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Irimia, R. L. Eoff, P. S. Pallan, F. P. Guengerich, and M. Egli Structure and Activity of Y-class DNA Polymerase DPO4 from Sulfolobus solfataricus with Templates Containing the Hydrophobic Thymine Analog 2,4-Difluorotoluene J. Biol. Chem., December 14, 2007; 282(50): 36421 - 36433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Yang and R. Woodgate What a difference a decade makes: Insights into translesion DNA synthesis PNAS, October 2, 2007; 104(40): 15591 - 15598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. d. Vega and M. Salas A highly conserved Tyrosine residue of family B DNA polymerases contributes to dictate translesion synthesis past 8-oxo-7,8-dihydro-2'-deoxyguanosine Nucleic Acids Res., August 1, 2007; (2007) gkm545v2. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Eoff, A. Irimia, K. C. Angel, M. Egli, and F. P. Guengerich Hydrogen Bonding of 7,8-Dihydro-8-oxodeoxyguanosine with a Charged Residue in the Little Finger Domain Determines Miscoding Events in Sulfolobus solfataricus DNA Polymerase Dpo4 J. Biol. Chem., July 6, 2007; 282(27): 19831 - 19843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Fiala and Z. Suo Sloppy Bypass of an Abasic Lesion Catalyzed by a Y-family DNA Polymerase J. Biol. Chem., March 16, 2007; 282(11): 8199 - 8206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Eoff, A. Irimia, M. Egli, and F. P. Guengerich Sulfolobus solfataricus DNA Polymerase Dpo4 Is Partially Inhibited by "Wobble" Pairing between O6-Methylguanine and Cytosine, but Accurate Bypass Is Preferred J. Biol. Chem., January 12, 2007; 282(2): 1456 - 1467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Choi, G. Chowdhury, H. Zang, K. C. Angel, C. C. Vu, L. A. Peterson, and F. P. Guengerich Translesion Synthesis across O6-Alkylguanine DNA Adducts by Recombinant Human DNA Polymerases J. Biol. Chem., December 15, 2006; 281(50): 38244 - 38256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Choi, K. C. Angel, and F. P. Guengerich Translesion Synthesis across Bulky N2-Alkyl Guanine DNA Adducts by Human DNA Polymerase {kappa} J. Biol. Chem., July 28, 2006; 281(30): 21062 - 21072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, O. Rechkoblit, L. Wang, D. J. Patel, R. Shapiro, and S. Broyde Mutagenic nucleotide incorporation and hindered translocation by a food carcinogen C8-dG adduct in Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): modeling and dynamics studies Nucleic Acids Res., July 4, 2006; 34(11): 3326 - 3337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. G. Duggin and S. D. Bell The Chromosome Replication Machinery of the Archaeon Sulfolobus solfataricus J. Biol. Chem., June 2, 2006; 281(22): 15029 - 15032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Kalam, K. Haraguchi, S. Chandani, E. L. Loechler, M. Moriya, M. M. Greenberg, and A. K. Basu Genetic effects of oxidative DNA damages: comparative mutagenesis of the imidazole ring-opened formamidopyrimidines (Fapy lesions) and 8-oxo-purines in simian kidney cells. Nucleic Acids Res., January 1, 2006; 34(8): 2305 - 2315. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |