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PDBsum entry 1u49
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Transferase/DNA
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PDB id
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1u49
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.2.7.7.7
- DNA-directed Dna polymerase.
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Reaction:
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DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
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DNA(n)
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+
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2'-deoxyribonucleoside 5'-triphosphate
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=
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DNA(n+1)
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+
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diphosphate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Nature
431:217-221
(2004)
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PubMed id:
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Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase.
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G.W.Hsu,
M.Ober,
T.Carell,
L.S.Beese.
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ABSTRACT
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Aerobic respiration generates reactive oxygen species that can damage guanine
residues and lead to the production of 8-oxoguanine (8oxoG), the major mutagenic
oxidative lesion in the genome. Oxidative damage is implicated in ageing and
cancer, and its prevalence presents a constant challenge to DNA polymerases that
ensure accurate transmission of genomic information. When these polymerases
encounter 8oxoG, they frequently catalyse misincorporation of adenine in
preference to accurate incorporation of cytosine. This results in the
propagation of G to T transversions, which are commonly observed somatic
mutations associated with human cancers. Here, we present sequential snapshots
of a high-fidelity DNA polymerase during both accurate and mutagenic replication
of 8oxoG. Comparison of these crystal structures reveals that 8oxoG induces an
inversion of the mismatch recognition mechanisms that normally proofread DNA,
such that the 8oxoG.adenine mismatch mimics a cognate base pair whereas the
8oxoG.cytosine base pair behaves as a mismatch. These studies reveal a
fundamental mechanism of error-prone replication and show how 8oxoG, and DNA
lesions in general, can form mismatches that evade polymerase error-detection
mechanisms, potentially leading to the stable incorporation of lethal mutations.
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Selected figure(s)
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Figure 1.
Figure 1: Modes of base pairing for 8oxoG. a, Oxidation of
guanine at C8 by reactive oxygen species (ROS). b, 8oxoG in a
Watson-Crick base pair with dC. Dashed lines indicate potential
hydrogen bonds. c, 8oxoG (syn) in a Hoogsteen base pair with dA
(anti).
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Figure 3.
Figure 3: Accurate translesion replication of 8oxoG by BF in
crystals. a, Schematic of BF active site. During replication,
the template base (n, red) moves from the pre-insertion site to
the post-insertion site to the DNA duplex binding region. b-d,
Structures of accurate 8oxoG replication (blue) are superimposed
with structures of unmodified guanine replication (grey). The
8oxoG template base (red) is shown at the pre-insertion site (b)
before nucleotide incorporation, the post-insertion site (c)
after dCTP incorporation, and the DNA duplex binding region (d)
after extension of C  8oxoG.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2004,
431,
217-221)
copyright 2004.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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D.Brégeon,
and
P.W.Doetsch
(2011).
Transcriptional mutagenesis: causes and involvement in tumour development.
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Nat Rev Cancer,
11,
218-227.
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G.P.McCallum,
M.Siu,
S.L.Ondovcik,
J.N.Sweeting,
and
P.G.Wells
(2011).
Methanol exposure does not lead to accumulation of oxidative DNA damage in bone marrow and spleen of mice, rabbits or primates.
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Mol Carcinog,
50,
163-172.
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G.P.McCallum,
M.Siu,
S.L.Ondovcik,
J.N.Sweeting,
and
P.G.Wells
(2011).
Methanol exposure does not lead to accumulation of oxidative DNA damage in bone marrow and spleen of mice, rabbits or primates.
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Mol Carcinog,
50,
163-172.
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K.N.Kirouac,
and
H.Ling
(2011).
Unique active site promotes error-free replication opposite an 8-oxo-guanine lesion by human DNA polymerase iota.
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Proc Natl Acad Sci U S A,
108,
3210-3215.
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PDB codes:
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P.Castillo,
M.Bogliolo,
and
J.Surralles
(2011).
Coordinated action of the Fanconi anemia and ataxia telangiectasia pathways in response to oxidative damage.
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DNA Repair (Amst),
10,
518-525.
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A.A.Golosov,
J.J.Warren,
L.S.Beese,
and
M.Karplus
(2010).
The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis.
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Structure,
18,
83-93.
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PDB codes:
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B.A.Flusberg,
D.R.Webster,
J.H.Lee,
K.J.Travers,
E.C.Olivares,
T.A.Clark,
J.Korlach,
and
S.W.Turner
(2010).
Direct detection of DNA methylation during single-molecule, real-time sequencing.
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Nat Methods,
7,
461-465.
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D.G.Passos-Silva,
M.A.Rajão,
P.H.Nascimento de Aguiar,
J.P.Vieira-da-Rocha,
C.R.Machado,
and
C.Furtado
(2010).
Overview of DNA Repair in Trypanosoma cruzi, Trypanosoma brucei, and Leishmania major.
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J Nucleic Acids,
2010,
840768.
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G.Pastor-Palacios,
E.Azuara-Liceaga,
and
L.G.Brieba
(2010).
A nuclear family A DNA polymerase from Entamoeba histolytica bypasses thymine glycol.
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PLoS Negl Trop Dis,
4,
e786.
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J.Beckman,
M.Wang,
G.Blaha,
J.Wang,
and
W.H.Konigsberg
(2010).
Substitution of Ala for Tyr567 in RB69 DNA polymerase allows dAMP to be inserted opposite 7,8-dihydro-8-oxoguanine .
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Biochemistry,
49,
4116-4125.
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PDB codes:
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M.Hori,
S.Yonekura,
T.Nohmi,
P.Gruz,
H.Sugiyama,
S.Yonei,
and
Q.M.Zhang-Akiyama
(2010).
Error-Prone Translesion DNA Synthesis by Escherichia coli DNA Polymerase IV (DinB) on Templates Containing 1,2-dihydro-2-oxoadenine.
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J Nucleic Acids,
2010,
807579.
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M.Münzel,
L.Lercher,
M.Müller,
and
T.Carell
(2010).
Chemical discrimination between dC and 5MedC via their hydroxylamine adducts.
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Nucleic Acids Res,
38,
e192.
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PDB code:
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M.T.Washington,
K.D.Carlson,
B.D.Freudenthal,
and
J.M.Pryor
(2010).
Variations on a theme: eukaryotic Y-family DNA polymerases.
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Biochim Biophys Acta,
1804,
1113-1123.
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P.Aller,
Y.Ye,
S.S.Wallace,
C.J.Burrows,
and
S.Doublié
(2010).
Crystal structure of a replicative DNA polymerase bound to the oxidized guanine lesion guanidinohydantoin.
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Biochemistry,
49,
2502-2509.
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PDB code:
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S.Obeid,
N.Blatter,
R.Kranaster,
A.Schnur,
K.Diederichs,
W.Welte,
and
A.Marx
(2010).
Replication through an abasic DNA lesion: structural basis for adenine selectivity.
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EMBO J,
29,
1738-1747.
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PDB codes:
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S.Yonekura,
U.Sanada,
and
Q.M.Zhang-Akiyama
(2010).
CiMutT, an asidian MutT homologue, has a 7, 8-dihydro-8-oxo-dGTP pyrophosphohydrolase activity responsible for sanitization of oxidized nucleotides in Ciona intestinalis.
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Genes Genet Syst,
85,
287-295.
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T.D.Silverstein,
R.Jain,
R.E.Johnson,
L.Prakash,
S.Prakash,
and
A.K.Aggarwal
(2010).
Structural basis for error-free replication of oxidatively damaged DNA by yeast DNA polymerase η.
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Structure,
18,
1463-1470.
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PDB codes:
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V.K.Batra,
W.A.Beard,
E.W.Hou,
L.C.Pedersen,
R.Prasad,
and
S.H.Wilson
(2010).
Mutagenic conformation of 8-oxo-7,8-dihydro-2'-dGTP in the confines of a DNA polymerase active site.
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Nat Struct Mol Biol,
17,
889-890.
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PDB code:
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A.Irimia,
R.L.Eoff,
F.P.Guengerich,
and
M.Egli
(2009).
Structural and functional elucidation of the mechanism promoting error-prone synthesis by human DNA polymerase kappa opposite the 7,8-dihydro-8-oxo-2'-deoxyguanosine adduct.
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J Biol Chem,
284,
22467-22480.
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PDB codes:
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C.Chen,
A.Zhang,
X.Zhang,
J.Hu,
and
L.X.Xu
(2009).
Numerical simulation of au nanoparticles effect on the PCR process.
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J Biomech Eng,
131,
074512.
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C.R.Arthur,
S.L.Morton,
L.D.Dunham,
P.M.Keeney,
and
J.P.Bennett
(2009).
Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance.
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Mol Neurodegener,
4,
37.
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E.J.Merino,
M.L.Davis,
and
J.K.Barton
(2009).
Common mitochondrial DNA mutations generated through DNA-mediated charge transport.
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Biochemistry,
48,
660-666.
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G.E.Damsma,
and
P.Cramer
(2009).
Molecular basis of transcriptional mutagenesis at 8-oxoguanine.
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J Biol Chem,
284,
31658-31663.
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PDB codes:
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J.J.Perry,
K.Hitomi,
and
J.A.Tainer
(2009).
Flexibility promotes fidelity.
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Structure,
17,
633-634.
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J.N.Patro,
M.Urban,
and
R.D.Kuchta
(2009).
Interaction of human DNA polymerase alpha and DNA polymerase I from Bacillus stearothermophilus with hypoxanthine and 8-oxoguanine nucleotides.
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Biochemistry,
48,
8271-8278.
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O.Rechkoblit,
L.Malinina,
Y.Cheng,
N.E.Geacintov,
S.Broyde,
and
D.J.Patel
(2009).
Impact of conformational heterogeneity of OxoG lesions and their pairing partners on bypass fidelity by Y family polymerases.
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Structure,
17,
725-736.
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PDB codes:
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P.Xu,
L.Oum,
Y.C.Lee,
N.E.Geacintov,
and
S.Broyde
(2009).
Visualizing sequence-governed nucleotide selectivities and mutagenic consequences through a replicative cycle: processing of a bulky carcinogen N2-dG lesion in a Y-family DNA polymerase.
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Biochemistry,
48,
4677-4690.
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Q.M.Zhang-Akiyama,
H.Morinaga,
M.Kikuchi,
S.Yonekura,
H.Sugiyama,
K.Yamamoto,
and
S.Yonei
(2009).
KsgA, a 16S rRNA adenine methyltransferase, has a novel DNA glycosylase/AP lyase activity to prevent mutations in Escherichia coli.
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Nucleic Acids Res,
37,
2116-2125.
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R.Vasquez-Del Carpio,
T.D.Silverstein,
S.Lone,
M.K.Swan,
J.R.Choudhury,
R.E.Johnson,
S.Prakash,
L.Prakash,
and
A.K.Aggarwal
(2009).
Structure of human DNA polymerase kappa inserting dATP opposite an 8-OxoG DNA lesion.
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PLoS One,
4,
e5766.
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PDB codes:
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S.D.McCulloch,
R.J.Kokoska,
P.Garg,
P.M.Burgers,
and
T.A.Kunkel
(2009).
The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases delta and eta.
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Nucleic Acids Res,
37,
2830-2840.
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S.Schneider,
S.Schorr,
and
T.Carell
(2009).
Crystal structure analysis of DNA lesion repair and tolerance mechanisms.
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Curr Opin Struct Biol,
19,
87-95.
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X.Meng,
Y.Zhou,
S.Zhang,
E.Y.Lee,
D.N.Frick,
and
M.Y.Lee
(2009).
DNA damage alters DNA polymerase delta to a form that exhibits increased discrimination against modified template bases and mismatched primers.
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Nucleic Acids Res,
37,
647-657.
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Y.Qi,
M.C.Spong,
K.Nam,
A.Banerjee,
S.Jiralerspong,
M.Karplus,
and
G.L.Verdine
(2009).
Encounter and extrusion of an intrahelical lesion by a DNA repair enzyme.
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Nature,
462,
762-766.
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PDB codes:
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A.Benz,
and
J.S.Hartig
(2008).
Redesigned tetrads with altered hydrogen bonding patterns enable programming of quadruplex topologies.
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Chem Commun (Camb),
(),
4010-4012.
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D.Vlcek,
A.Sevcovicová,
B.Sviezená,
E.Gálová,
and
E.Miadoková
(2008).
Chlamydomonas reinhardtii: a convenient model system for the study of DNA repair in photoautotrophic eukaryotes.
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Curr Genet,
53,
1.
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R.Venkatramani,
and
R.Radhakrishnan
(2008).
Effect of oxidatively damaged DNA on the active site preorganization during nucleotide incorporation in a high fidelity polymerase from Bacillus stearothermophilus.
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Proteins,
71,
1360-1372.
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S.Broyde,
L.Wang,
O.Rechkoblit,
N.E.Geacintov,
and
D.J.Patel
(2008).
Lesion processing: high-fidelity versus lesion-bypass DNA polymerases.
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Trends Biochem Sci,
33,
209-219.
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C.T.Radom,
A.Banerjee,
and
G.L.Verdine
(2007).
Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutations.
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J Biol Chem,
282,
9182-9194.
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PDB codes:
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M.A.Graziewicz,
R.J.Bienstock,
and
W.C.Copeland
(2007).
The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine.
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Hum Mol Genet,
16,
2729-2739.
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M.Garcia-Diaz,
and
K.Bebenek
(2007).
Multiple functions of DNA polymerases.
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CRC Crit Rev Plant Sci,
26,
105-122.
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M.de Vega,
and
M.Salas
(2007).
A highly conserved Tyrosine residue of family B DNA polymerases contributes to dictate translesion synthesis past 8-oxo-7,8-dihydro-2'-deoxyguanosine.
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Nucleic Acids Res,
35,
5096-5107.
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R.L.Eoff,
A.Irimia,
K.C.Angel,
M.Egli,
and
F.P.Guengerich
(2007).
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.
|
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J Biol Chem,
282,
19831-19843.
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PDB codes:
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S.S.David,
V.L.O'Shea,
and
S.Kundu
(2007).
Base-excision repair of oxidative DNA damage.
|
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Nature,
447,
941-950.
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S.Yonekura,
N.Nakamura,
T.Doi,
H.Sugiyama,
K.Yamamoto,
S.Yonei,
and
Q.M.Zhang
(2007).
Recombinant Schizosaccharomyces pombe Nth1 protein exhibits DNA glycosylase activities for 8-oxo-7,8-dihydroguanine and thymine residues oxidized in the methyl group.
|
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J Radiat Res (Tokyo),
48,
417-424.
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X.Zhao,
J.G.Muller,
M.Halasyam,
S.S.David,
and
C.J.Burrows
(2007).
In vitro ligation of oligodeoxynucleotides containing C8-oxidized purine lesions using bacteriophage T4 DNA ligase.
|
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Biochemistry,
46,
3734-3744.
|
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Y.Wang,
S.Reddy,
W.A.Beard,
S.H.Wilson,
and
T.Schlick
(2007).
Differing conformational pathways before and after chemistry for insertion of dATP versus dCTP opposite 8-oxoG in DNA polymerase beta.
|
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Biophys J,
92,
3063-3070.
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Y.Wang,
and
T.Schlick
(2007).
Distinct energetics and closing pathways for DNA polymerase beta with 8-oxoG template and different incoming nucleotides.
|
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BMC Struct Biol,
7,
7.
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Y.Yamaguchi,
T.Mura,
S.Chanarat,
S.Okamoto,
and
H.Handa
(2007).
Hepatitis delta antigen binds to the clamp of RNA polymerase II and affects transcriptional fidelity.
|
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Genes Cells,
12,
863-875.
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A.Banerjee,
and
G.L.Verdine
(2006).
A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex.
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Proc Natl Acad Sci U S A,
103,
15020-15025.
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PDB code:
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A.Sakai,
M.Nakanishi,
K.Yoshiyama,
and
H.Maki
(2006).
Impact of reactive oxygen species on spontaneous mutagenesis in Escherichia coli.
|
| |
Genes Cells,
11,
767-778.
|
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E.Pienaar,
M.Theron,
M.Nelson,
and
H.J.Viljoen
(2006).
A quantitative model of error accumulation during PCR amplification.
|
| |
Comput Biol Chem,
30,
102-111.
|
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H.O.Sintim,
and
E.T.Kool
(2006).
Remarkable sensitivity to DNA base shape in the DNA polymerase active site.
|
| |
Angew Chem Int Ed Engl,
45,
1974-1979.
|
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|
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H.Zang,
A.Irimia,
J.Y.Choi,
K.C.Angel,
L.V.Loukachevitch,
M.Egli,
and
F.P.Guengerich
(2006).
Efficient and high fidelity incorporation of dCTP opposite 7,8-dihydro-8-oxodeoxyguanosine by Sulfolobus solfataricus DNA polymerase Dpo4.
|
| |
J Biol Chem,
281,
2358-2372.
|
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|
PDB codes:
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J.J.Warren,
L.J.Forsberg,
and
L.S.Beese
(2006).
The structural basis for the mutagenicity of O(6)-methyl-guanine lesions.
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| |
Proc Natl Acad Sci U S A,
103,
19701-19706.
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PDB codes:
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M.Kakoki,
C.M.Kizer,
X.Yi,
N.Takahashi,
H.S.Kim,
C.R.Bagnell,
C.J.Edgell,
N.Maeda,
J.C.Jennette,
and
O.Smithies
(2006).
Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors.
|
| |
J Clin Invest,
116,
1302-1309.
|
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|
O.Rechkoblit,
L.Malinina,
Y.Cheng,
V.Kuryavyi,
S.Broyde,
N.E.Geacintov,
and
D.J.Patel
(2006).
Stepwise translocation of Dpo4 polymerase during error-free bypass of an oxoG lesion.
|
| |
PLoS Biol,
4,
e11.
|
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|
PDB codes:
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R.P.Clausen
(2006).
Organic chemistry at the interface to biology.
|
| |
Chembiochem,
7,
845-849.
|
|
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|
|
A.A.Ishchenko,
X.Yang,
D.Ramotar,
and
M.Saparbaev
(2005).
The 3'->5' exonuclease of Apn1 provides an alternative pathway to repair 7,8-dihydro-8-oxodeoxyguanosine in Saccharomyces cerevisiae.
|
| |
Mol Cell Biol,
25,
6380-6390.
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|
D.T.Nair,
R.E.Johnson,
L.Prakash,
S.Prakash,
and
A.K.Aggarwal
(2005).
Human DNA polymerase iota incorporates dCTP opposite template G via a G.C + Hoogsteen base pair.
|
| |
Structure,
13,
1569-1577.
|
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|
PDB code:
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G.W.Hsu,
X.Huang,
N.P.Luneva,
N.E.Geacintov,
and
L.S.Beese
(2005).
Structure of a high fidelity DNA polymerase bound to a benzo[a]pyrene adduct that blocks replication.
|
| |
J Biol Chem,
280,
3764-3770.
|
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|
PDB code:
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J.D.Ahle,
S.Barr,
A.M.Chin,
and
T.R.Battersby
(2005).
Sequence determination of nucleic acids containing 5-methylisocytosine and isoguanine: identification and insight into polymerase replication of the non-natural nucleobases.
|
| |
Nucleic Acids Res,
33,
3176-3184.
|
|
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|
|
K.D.Carlson,
and
M.T.Washington
(2005).
Mechanism of efficient and accurate nucleotide incorporation opposite 7,8-dihydro-8-oxoguanine by Saccharomyces cerevisiae DNA polymerase eta.
|
| |
Mol Cell Biol,
25,
2169-2176.
|
|
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|
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|
L.G.Brieba,
R.J.Kokoska,
K.Bebenek,
T.A.Kunkel,
and
T.Ellenberger
(2005).
A lysine residue in the fingers subdomain of T7 DNA polymerase modulates the miscoding potential of 8-oxo-7,8-dihydroguanosine.
|
| |
Structure,
13,
1653-1659.
|
|
|
PDB code:
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N.Oka,
and
M.M.Greenberg
(2005).
The effect of the 2-amino group of 7,8-dihydro-8-oxo-2'-deoxyguanosine on translesion synthesis and duplex stability.
|
| |
Nucleic Acids Res,
33,
1637-1643.
|
|
|
|
|
|
|
P.Das,
and
G.B.Schuster
(2005).
Effect of condensate formation on long-distance radical cation migration in DNA.
|
| |
Proc Natl Acad Sci U S A,
102,
14227-14231.
|
|
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|
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|
|
T.Doi,
S.Yonekura,
K.Tano,
S.Yasuhira,
S.Yonei,
and
Q.M.Zhang
(2005).
The Shizosaccharomyces pombe homolog (SpMYH) of the Escherichia coli MutY is required for removal of guanine from 8-oxoguanine/guanine mispairs to prevent G:C to C:G transversions.
|
| |
J Radiat Res (Tokyo),
46,
205-214.
|
|
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|
V.K.Batra,
W.A.Beard,
D.D.Shock,
L.C.Pedersen,
and
S.H.Wilson
(2005).
Nucleotide-induced DNA polymerase active site motions accommodating a mutagenic DNA intermediate.
|
| |
Structure,
13,
1225-1233.
|
|
|
PDB codes:
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|
W.A.Beard,
and
S.H.Wilson
(2005).
Syn-full behavior by T7 DNA polymerase.
|
| |
Structure,
13,
1580-1582.
|
|
|
|
|
|
|
G.W.Hsu,
J.R.Kiefer,
D.Burnouf,
O.J.Becherel,
R.P.Fuchs,
and
L.S.Beese
(2004).
Observing translesion synthesis of an aromatic amine DNA adduct by a high-fidelity DNA polymerase.
|
| |
J Biol Chem,
279,
50280-50285.
|
|
|
PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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|
Links
