Biochemistry
Article
(5) Sowers, L. C., Goodman, M. F., Eritja, R., Kaplan, B., and
Fazakerley, G. V. (1989) Ionized and wobble base-pairing for
bromouracil-guanine in equilibrium under physiological conditions.
A nuclear magnetic resonance study on an oligonucleotide containing
a bromouracil-guanine base-pair as a function of pH. J. Mol. Biol. 205,
437−447.
(20) Upton, T. G., Kashemirov, B. A., McKenna, C. E., Goodman, M.
F., Prakash, G. K., Kultyshev, R., Batra, V. K., Shock, D. D., Pedersen,
L. C., Beard, W. A., and Wilson, S. H. (2009) Alpha,beta-
difluoromethylene deoxynucleoside 5′-triphosphates: A convenient
synthesis of useful probes for DNA polymerase beta structure and
function. Org. Lett. 11, 1883−1886.
(6) Batra, V. K., Shock, D. D., Beard, W. A., McKenna, C. E., and
Wilson, S. H. (2012) Binary complex crystal structure of DNA
polymerase beta reveals multiple conformations of the templating 8-
oxoguanine lesion. Proc. Natl. Acad. Sci. U.S.A. 109, 113−118.
(7) Hsu, G. W., Ober, M., Carell, T., and Beese, L. S. (2004) Error-
prone replication of oxidatively damaged DNA by a high-fidelity DNA
polymerase. Nature 431, 217−221.
(21) Joyce, C. M., and Benkovic, S. J. (2004) DNA polymerase
fidelity: Kinetics, structure, and checkpoints. Biochemistry 43, 14317−
14324.
(22) Bakhtina, M., Roettger, M. P., and Tsai, M. D. (2009)
Contribution of the reverse rate of the conformational step to
polymerase beta fidelity. Biochemistry 48, 3197−3208.
(23) Liu, J., and Tsai, M. D. (2001) DNA polymerase beta: Pre-
steady-state kinetic analyses of dATP alpha S stereoselectivity and
alteration of the stereoselectivity by various metal ions and by site-
directed mutagenesis. Biochemistry 40, 9014−9022.
(24) Roettger, M. P., Bakhtina, M., and Tsai, M. D. (2008)
Mismatched and matched dNTP incorporation by DNA polymerase
beta proceed via analogous kinetic pathways. Biochemistry 47, 9718−
9727.
(25) Beard, W. A., and Wilson, S. H. (2006) Structure and
mechanism of DNA polymerase beta. Chem Rev 106, 361−382.
(26) Canitrot, Y., Frechet, M., Servant, L., Cazaux, C., and Hoffmann,
J. S. (1999) Overexpression of DNA polymerase beta: A genomic
instability enhancer process. FASEB J. 13, 1107−1111.
(8) Kunkel, T. A., and Bebenek, K. (2000) DNA replication fidelity.
Annu. Rev. Biochem. 69, 497−529.
(9) Tippin, B., Kobayashi, S., Bertram, J. G., and Goodman, M. F.
(2004) To slip or skip, visualizing frameshift mutation dynamics for
error-prone DNA polymerases. J. Biol. Chem. 279, 45360−45368.
(10) Batra, V. K., Beard, W. A., Shock, D. D., Pedersen, L. C., and
Wilson, S. H. (2005) Nucleotide-induced DNA polymerase active site
motions accommodating a mutagenic DNA intermediate. Structure 13,
1225−1233.
(11) Cuniasse, P., Sowers, L. C., Eritja, R., Kaplan, B., Goodman, M.
F., Cognet, J. A., Le Bret, M., Guschlbauer, W., and Fazakerley, G. V.
(1989) Abasic frameshift in DNA. Solution conformation determined
by proton NMR and molecular mechanics calculations. Biochemistry
28, 2018−2026.
(12) Tang, Y., Liu, Z., Ding, S., Lin, C. H., Cai, Y., Rodriguez, F. A.,
Sayer, J. M., Jerina, D. M., Amin, S., Broyde, S., and Geacintov, N. E.
(2012) Nuclear magnetic resonance solution structure of an N(2)-
guanine DNA adduct derived from the potent tumorigen dibenzo-
[a,l]pyrene: Intercalation from the minor groove with ruptured
Watson-Crick base pairing. Biochemistry 51, 9751−9762.
(13) Wang, W., Hellinga, H. W., and Beese, L. S. (2011) Structural
evidence for the rare tautomer hypothesis of spontaneous mutagenesis.
Proc. Natl. Acad. Sci. U.S.A. 108, 17644−17648.
(27) Lang, T., Maitra, M., Starcevic, D., Li, S. X., and Sweasy, J. B.
(2004) A DNA polymerase beta mutant from colon cancer cells
induces mutations. Proc. Natl. Acad. Sci. U.S.A. 101, 6074−6079.
(28) Starcevic, D., Dalal, S., and Sweasy, J. B. (2004) Is there a link
between DNA polymerase beta and cancer? Cell Cycle 3, 998−1001.
(29) Wang, L., Patel, U., Ghosh, L., and Banerjee, S. (1992) DNA
polymerase beta mutations in human colorectal cancer. Cancer Res. 52,
4824−4827.
(30) Chamberlain, B. T., Upton, T. G., Kashemirov, B. A., and
McKenna, C. E. (2011) Alpha-azido bisphosphonates: Synthesis and
nucleotide analogues. J. Org. Chem. 76, 5132−5136.
(31) Wu, Y., Zakharova, V. M., Kashemirov, B. A., Goodman, M. F.,
Batra, V. K., Wilson, S. H., and McKenna, C. E. (2012) Beta,gamma-
CHF- and beta,gamma-CHCl-dGTP diastereomers: Synthesis, discrete
31P NMR signatures, and absolute configurations of new stereo-
chemical probes for DNA polymerases. J. Am. Chem. Soc. 134, 8734−
8737.
(32) Braun-Sand, S., Olsson, M. H. M., and Warshel, A. (2005)
Computer modeling of enzyme catalysis and its relationship to
concepts in physical organic chemistry. Adv. Phys. Org. Chem. 40, 201−
245.
(33) Schweins, T., Geyer, M., Kalbitzer, H. R., Wittinghofer, A., and
Warshel, A. (1996) Linear free energy relationships in the intrinsic and
GTPase activating protein-stimulated guanosine 5′-triphosphate
hydrolysis of p21ras. Biochemistry 35, 14225−14231.
(34) Jencks, W. P. (1987) Effects of solvation on nucleophilic
reactivity in hydroxylic solvents: Decreasing reactivity with increasing
basicity. Nucleophilicity 215, 155−167.
(35) Alexandrova, L. A., Skoblov, A. Y., Jasko, M. V., Victorova, L. S.,
and Krayevsky, A. A. (1998) 2′-Deoxynucleoside 5′-triphosphates
modified at alpha-, beta- and gamma-phosphates as substrates for
DNA polymerases. Nucleic Acids Res. 26, 778−786.
(36) Martynov, B. I., Shirokova, E. A., Jasko, M. V., Victorova, L. S.,
and Krayevsky, A. A. (1997) Effect of triphosphate modifications in 2′-
deoxynucleoside 5′-triphosphates on their specificity towards various
DNA polymerases. FEBS Lett. 410, 423−427.
(37) Moffatt, J. G., and Khorana, H. G. (1961) Nucleoside
polyphosphates: The synthesis and some reactions of nucleoside 5′-
phosphoromorpholidates and related compounds. Improved methods
for the preparation of nucleoside 5′-polyphosphates. J. Am. Chem. Soc.
83, 649−658.
(38) Moffatt, J. G. (1964) General synthesis of nucleoside 5′-
triphosphates. Can. J. Chem. 42, 599−604.
(14) Batra, V. K., Pedersen, L. C., Beard, W. A., Wilson, S. H.,
Kashemirov, B. A., Upton, T. G., Goodman, M. F., and McKenna, C.
E. (2010) Halogenated beta,gamma-methylene- and ethylidene-dGTP-
DNA ternary complexes with DNA polymerase beta: Structural
evidence for stereospecific binding of the fluoromethylene analogues. J.
Am. Chem. Soc. 132, 7617−7625.
(15) Chamberlain, B. T., Batra, V. K., Beard, W. A., Kadina, A. P.,
Shock, D. D., Kashemirov, B. A., McKenna, C. E., Goodman, M. F.,
and Wilson, S. H. (2012) Stereospecific formation of a ternary
complex of (S)-alpha,beta-fluoromethylene-dATP with DNA pol beta.
ChemBioChem 13, 528−530.
(16) McKenna, C. E., Kashemirov, B. A., Upton, T. G., Batra, V. K.,
Goodman, M. F., Pedersen, L. C., Beard, W. A., and Wilson, S. H.
(2007) (R)-Beta,gamma-fluoromethylene-dGTP-DNA ternary com-
plex with DNA polymerase beta. J. Am. Chem. Soc. 129, 15412−15413.
(17) Oertell, K., Wu, Y., Zakharova, V. M., Kashemirov, B. A., Shock,
D. D., Beard, W. A., Wilson, S. H., McKenna, C. E., and Goodman, M.
F. (2012) Effect of beta,gamma-CHF- and beta,gamma-CHCl-dGTP
halogen atom stereochemistry on the transition state of DNA
polymerase beta. Biochemistry 51, 8491−8501.
(18) Sucato, C. A., Upton, T. G., Kashemirov, B. A., Batra, V. K.,
Martinek, V., Xiang, Y., Beard, W. A., Pedersen, L. C., Wilson, S. H.,
McKenna, C. E., Florian, J., Warshel, A., and Goodman, M. F. (2007)
Modifying the beta,gamma leaving-group bridging oxygen alters
nucleotide incorporation efficiency, fidelity, and the catalytic
mechanism of DNA polymerase beta. Biochemistry 46, 461−471.
(19) Sucato, C. A., Upton, T. G., Kashemirov, B. A., Osuna, J.,
Oertell, K., Beard, W. A., Wilson, S. H., Florian, J., Warshel, A.,
McKenna, C. E., and Goodman, M. F. (2008) DNA polymerase beta
fidelity: Halomethylene-modified leaving groups in pre-steady-state
kinetic analysis reveal differences at the chemical transition state.
Biochemistry 47, 870−879.
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dx.doi.org/10.1021/bi500101z | Biochemistry 2014, 53, 1842−1848