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* Residue conservation analysis
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Enzyme class:
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Chain D:
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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Cell
99:155-166
(1999)
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PubMed id:
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Building a replisome from interacting pieces: sliding clamp complexed to a peptide from DNA polymerase and a polymerase editing complex.
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Y.Shamoo,
T.A.Steitz.
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ABSTRACT
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We have solved the crystal structures of the bacteriophage RB69 sliding clamp,
its complex with a peptide essential for DNA polymerase interactions, and the
DNA polymerase complexed with primer-template DNA. The editing complex structure
shows a partially melted duplex DNA exiting from the exonuclease domain at an
unexpected angle and significant changes in the protein structure. The clamp
complex shows the C-terminal 11 residues of polymerase bound in a hydrophobic
pocket, and it allows docking of the editing and clamp structures together. The
peptide binds to the sliding clamp at a position identical to that of a
replication inhibitor peptide bound to PCNA, suggesting that the replication
inhibitor protein p21CIP1 functions by competing with eukaryotic polymerases for
the same binding pocket on the clamp.
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Selected figure(s)
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Figure 3.
Figure 3. Peptide Interactions with the Sliding ClampThe
interaction of pol-CT with RB69 sliding clamp is close fitting
and consists mainly of hydrophobic interactions. Accessible
surface of RB69 sliding clamp is shown in blue, while pol-CT is
displayed as a stick model. To illustrate the pol-CT-binding
pocket, all the sliding clamp surfaces within 4.5 Å of the
pol-CT model are colored in yellow. The figure was made using
GRASP ([37]).
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Figure 4.
Figure 4. Residues of the T4 and RB69 Pol-CTs that Are
Similar to the ClampResidues in the RB69 pol-CT that are colored
in blue are different in the T4 pol-CT. Residues that are the
same in T4 and RB69 are shown in red. Residues that differ point
away from the pol-CT-binding pocket (Table 1).
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The above figures are
reprinted
by permission from Cell Press:
Cell
(1999,
99,
155-166)
copyright 1999.
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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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C.J.Hansen,
L.Wu,
J.D.Fox,
B.Arezi,
and
H.H.Hogrefe
(2011).
Engineered split in Pfu DNA polymerase fingers domain improves incorporation of nucleotide gamma-phosphate derivative.
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| |
Nucleic Acids Res,
39,
1801-1810.
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K.Mayanagi,
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M.Saito,
D.Kohda,
Y.Ishino,
T.Shirai,
and
K.Morikawa
(2011).
Architecture of the DNA polymerase B-proliferating cell nuclear antigen (PCNA)-DNA ternary complex.
|
| |
Proc Natl Acad Sci U S A,
108,
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S.K.Jozwiakowski,
and
B.A.Connolly
(2011).
A modified family-B archaeal DNA polymerase with reverse transcriptase activity.
|
| |
Chembiochem,
12,
35-37.
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Y.W.Yin
(2011).
Structural insight on processivity, human disease and antiviral drug toxicity.
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| |
Curr Opin Struct Biol,
21,
83-91.
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E.Johansson,
and
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(2010).
The eukaryotic replicative DNA polymerases take shape.
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| |
Trends Biochem Sci,
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E.P.Geiduschek,
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| |
Virol J,
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Biochim Biophys Acta,
1804,
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J.Rudnicki,
J.Midkiff,
L.Reha-Krantz,
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and
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(2010).
Kinetics of mismatch formation opposite lesions by the replicative DNA polymerase from bacteriophage RB69.
|
| |
Biochemistry,
49,
2317-2325.
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PDB code:
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T.C.Mueser,
J.M.Hinerman,
J.M.Devos,
R.A.Boyer,
and
K.J.Williams
(2010).
Structural analysis of bacteriophage T4 DNA replication: a review in the Virology Journal series on bacteriophage T4 and its relatives.
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Virol J,
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X.Meng,
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and
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(2010).
The p12 subunit of human polymerase delta modulates the rate and fidelity of DNA synthesis.
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| |
Biochemistry,
49,
3545-3554.
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|
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Z.Zhuang,
and
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(2010).
Processivity factor of DNA polymerase and its expanding role in normal and translesion DNA synthesis.
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Biochim Biophys Acta,
1804,
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and
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Proofreading dynamics of a processive DNA polymerase.
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EMBO J,
28,
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E.P.Tchesnokov,
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and
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Engineering of a chimeric RB69 DNA polymerase sensitive to drugs targeting the cytomegalovirus enzyme.
|
| |
J Biol Chem,
284,
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F.J.López de Saro
(2009).
Regulation of interactions with sliding clamps during DNA replication and repair.
|
| |
Curr Genomics,
10,
206-215.
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G.A.Cisneros,
L.Perera,
R.M.Schaaper,
L.C.Pedersen,
R.E.London,
L.G.Pedersen,
and
T.A.Darden
(2009).
Reaction mechanism of the epsilon subunit of E. coli DNA polymerase III: insights into active site metal coordination and catalytically significant residues.
|
| |
J Am Chem Soc,
131,
1550-1556.
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H.J.Russell,
T.T.Richardson,
K.Emptage,
and
B.A.Connolly
(2009).
The 3'-5' proofreading exonuclease of archaeal family-B DNA polymerase hinders the copying of template strand deaminated bases.
|
| |
Nucleic Acids Res,
37,
7603-7611.
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H.Nishida,
K.Mayanagi,
S.Kiyonari,
Y.Sato,
T.Oyama,
Y.Ishino,
and
K.Morikawa
(2009).
Structural determinant for switching between the polymerase and exonuclease modes in the PCNA-replicative DNA polymerase complex.
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| |
Proc Natl Acad Sci U S A,
106,
20693-20698.
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H.Zhang,
J.Beckman,
J.Wang,
and
W.Konigsberg
(2009).
RB69 DNA polymerase mutants with expanded nascent base-pair-binding pockets are highly efficient but have reduced base selectivity.
|
| |
Biochemistry,
48,
6940-6950.
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I.Rodríguez,
J.M.Lázaro,
M.Salas,
and
M.de Vega
(2009).
Involvement of the TPR2 subdomain movement in the activities of phi29 DNA polymerase.
|
| |
Nucleic Acids Res,
37,
193-203.
|
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K.Datta,
N.P.Johnson,
V.J.Licata,
and
P.H.von Hippel
(2009).
Local Conformations and Competitive Binding Affinities of Single- and Double-stranded Primer-Template DNA at the Polymerization and Editing Active Sites of DNA Polymerases.
|
| |
J Biol Chem,
284,
17180-17193.
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K.Murayama,
S.Nakayama,
M.Kato-Murayama,
R.Akasaka,
N.Ohbayashi,
Y.Kamewari-Hayami,
T.Terada,
M.Shirouzu,
T.Tsurumi,
and
S.Yokoyama
(2009).
Crystal structure of epstein-barr virus DNA polymerase processivity factor BMRF1.
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J Biol Chem,
284,
35896-35905.
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PDB code:
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L.B.Bloom
(2009).
Loading clamps for DNA replication and repair.
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DNA Repair (Amst),
8,
570-578.
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|
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|
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M.Wang,
H.R.Lee,
and
W.Konigsberg
(2009).
Effect of A and B metal ion site occupancy on conformational changes in an RB69 DNA polymerase ternary complex.
|
| |
Biochemistry,
48,
2075-2086.
|
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|
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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.
|
| |
Nucleic Acids Res,
37,
2830-2840.
|
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|
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|
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S.M.Hamdan,
and
C.C.Richardson
(2009).
Motors, switches, and contacts in the replisome.
|
| |
Annu Rev Biochem,
78,
205-243.
|
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|
|
|
|
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S.Puthenveetil,
D.S.Liu,
K.A.White,
S.Thompson,
and
A.Y.Ting
(2009).
Yeast display evolution of a kinetically efficient 13-amino acid substrate for lipoic acid ligase.
|
| |
J Am Chem Soc,
131,
16430-16438.
|
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|
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|
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W.Strzalka,
T.Oyama,
K.Tori,
and
K.Morikawa
(2009).
Crystal structures of the Arabidopsis thaliana proliferating cell nuclear antigen 1 and 2 proteins complexed with the human p21 C-terminal segment.
|
| |
Protein Sci,
18,
1072-1080.
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PDB codes:
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A.Garcia-Maruniak,
J.E.Maruniak,
W.Farmerie,
and
D.G.Boucias
(2008).
Sequence analysis of a non-classified, non-occluded DNA virus that causes salivary gland hypertrophy of Musca domestica, MdSGHV.
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| |
Virology,
377,
184-196.
|
 |
|
|
|
|
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A.M.Abd-Alla,
F.Cousserans,
A.G.Parker,
J.A.Jehle,
N.J.Parker,
J.M.Vlak,
A.S.Robinson,
and
M.Bergoin
(2008).
Genome analysis of a Glossina pallidipes salivary gland hypertrophy virus reveals a novel, large, double-stranded circular DNA virus.
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| |
J Virol,
82,
4595-4611.
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|
|
|
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G.Komazin-Meredith,
W.L.Santos,
D.J.Filman,
J.M.Hogle,
G.L.Verdine,
and
D.M.Coen
(2008).
The positively charged surface of herpes simplex virus UL42 mediates DNA binding.
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| |
J Biol Chem,
283,
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|
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J.Hubscher,
L.Luthy,
B.Berger-Bachi,
and
P.Stutzmann Meier
(2008).
Phylogenetic distribution and membrane topology of the LytR-CpsA-Psr protein family.
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| |
BMC Genomics,
9,
617.
|
 |
|
|
|
|
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K.F.Bryant,
and
D.M.Coen
(2008).
Inhibition of translation by a short element in the 5' leader of the herpes simplex virus 1 DNA polymerase transcript.
|
| |
J Virol,
82,
77-85.
|
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|
|
|
|
 |
P.Kukreti,
K.Singh,
A.Ketkar,
and
M.J.Modak
(2008).
Identification of a new motif required for the 3'-5' exonuclease activity of Escherichia coli DNA polymerase I (Klenow fragment): the RRRY motif is necessary for the binding of single-stranded DNA substrate and the template strand of the mismatched duplex.
|
| |
J Biol Chem,
283,
17979-17990.
|
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|
|
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|
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R.E.Georgescu,
S.S.Kim,
O.Yurieva,
J.Kuriyan,
X.P.Kong,
and
M.O'Donnell
(2008).
Structure of a sliding clamp on DNA.
|
| |
Cell,
132,
43-54.
|
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|
PDB code:
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|
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S.Nechaev,
and
E.P.Geiduschek
(2008).
Dissection of the bacteriophage T4 late promoter complex.
|
| |
J Mol Biol,
379,
402-413.
|
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|
|
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|
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X.Chen,
T.P.Patel,
V.I.Simirskii,
and
M.K.Duncan
(2008).
PCNA interacts with Prox1 and represses its transcriptional activity.
|
| |
Mol Vis,
14,
2076-2086.
|
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|
|
|
|
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A.Jacewicz,
K.Makiela,
A.Kierzek,
J.W.Drake,
and
A.Bebenek
(2007).
The roles of Tyr391 and Tyr619 in RB69 DNA polymerase replication fidelity.
|
| |
J Mol Biol,
368,
18-29.
|
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|
|
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|
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E.Fidalgo da Silva,
and
L.J.Reha-Krantz
(2007).
DNA polymerase proofreading: active site switching catalyzed by the bacteriophage T4 DNA polymerase.
|
| |
Nucleic Acids Res,
35,
5452-5463.
|
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|
|
|
|
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H.Zhang,
W.Cao,
E.Zakharova,
W.Konigsberg,
and
E.M.De La Cruz
(2007).
Fluorescence of 2-aminopurine reveals rapid conformational changes in the RB69 DNA polymerase-primer/template complexes upon binding and incorporation of matched deoxynucleoside triphosphates.
|
| |
Nucleic Acids Res,
35,
6052-6062.
|
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|
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J.M.Devos,
S.J.Tomanicek,
C.E.Jones,
N.G.Nossal,
and
T.C.Mueser
(2007).
Crystal structure of bacteriophage T4 5' nuclease in complex with a branched DNA reveals how flap endonuclease-1 family nucleases bind their substrates.
|
| |
J Biol Chem,
282,
31713-31724.
|
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PDB code:
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|
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M.Garcia-Diaz,
and
K.Bebenek
(2007).
Multiple functions of DNA polymerases.
|
| |
CRC Crit Rev Plant Sci,
26,
105-122.
|
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|
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M.Hogg,
P.Aller,
W.Konigsberg,
S.S.Wallace,
and
S.Doublié
(2007).
Structural and biochemical investigation of the role in proofreading of a beta hairpin loop found in the exonuclease domain of a replicative DNA polymerase of the B family.
|
| |
J Biol Chem,
282,
1432-1444.
|
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PDB code:
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N.Schormann,
A.Grigorian,
A.Samal,
R.Krishnan,
L.DeLucas,
and
D.Chattopadhyay
(2007).
Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly.
|
| |
BMC Struct Biol,
7,
45.
|
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PDB codes:
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A.S.Doré,
M.L.Kilkenny,
S.A.Jones,
A.W.Oliver,
S.M.Roe,
S.D.Bell,
and
L.H.Pearl
(2006).
Structure of an archaeal PCNA1-PCNA2-FEN1 complex: elucidating PCNA subunit and client enzyme specificity.
|
| |
Nucleic Acids Res,
34,
4515-4526.
|
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|
PDB code:
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|
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B.A.Appleton,
J.Brooks,
A.Loregian,
D.J.Filman,
D.M.Coen,
and
J.M.Hogle
(2006).
Crystal structure of the cytomegalovirus DNA polymerase subunit UL44 in complex with the C terminus from the catalytic subunit. Differences in structure and function relative to unliganded UL44.
|
| |
J Biol Chem,
281,
5224-5232.
|
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|
PDB code:
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|
 |
C.Indiani,
and
M.O'Donnell
(2006).
The replication clamp-loading machine at work in the three domains of life.
|
| |
Nat Rev Mol Cell Biol,
7,
751-761.
|
 |
|
|
|
|
 |
G.Andrei,
D.B.Gammon,
P.Fiten,
E.De Clercq,
G.Opdenakker,
R.Snoeck,
and
D.H.Evans
(2006).
Cidofovir resistance in vaccinia virus is linked to diminished virulence in mice.
|
| |
J Virol,
80,
9391-9401.
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I.Ivanov,
B.R.Chapados,
J.A.McCammon,
and
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(2006).
Proliferating cell nuclear antigen loaded onto double-stranded DNA: dynamics, minor groove interactions and functional implications.
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| |
Nucleic Acids Res,
34,
6023-6033.
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|
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M.A.Argiriadi,
E.R.Goedken,
I.Bruck,
M.O'Donnell,
and
J.Kuriyan
(2006).
Crystal structure of a DNA polymerase sliding clamp from a Gram-positive bacterium.
|
| |
BMC Struct Biol,
6,
2.
|
 |
|
PDB code:
|
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|
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|
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M.Hogg,
W.Cooper,
L.Reha-Krantz,
and
S.S.Wallace
(2006).
Kinetics of error generation in homologous B-family DNA polymerases.
|
| |
Nucleic Acids Res,
34,
2528-2535.
|
 |
|
|
|
|
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R.S.Kornbluth,
D.F.Smee,
R.W.Sidwell,
V.Snarsky,
D.H.Evans,
and
K.Y.Hostetler
(2006).
Mutations in the E9L polymerase gene of cidofovir-resistant vaccinia virus strain WR are associated with the drug resistance phenotype.
|
| |
Antimicrob Agents Chemother,
50,
4038-4043.
|
 |
|
|
|
|
 |
R.Shi,
A.Azzi,
C.Gilbert,
G.Boivin,
and
S.X.Lin
(2006).
Three-dimensional modeling of cytomegalovirus DNA polymerase and preliminary analysis of drug resistance.
|
| |
Proteins,
64,
301-307.
|
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|
|
|
|
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S.Liu,
J.D.Knafels,
J.S.Chang,
G.A.Waszak,
E.T.Baldwin,
M.R.Deibel,
D.R.Thomsen,
F.L.Homa,
P.A.Wells,
M.C.Tory,
R.A.Poorman,
H.Gao,
X.Qiu,
and
A.P.Seddon
(2006).
Crystal structure of the herpes simplex virus 1 DNA polymerase.
|
| |
J Biol Chem,
281,
18193-18200.
|
 |
|
PDB code:
|
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|
|
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|
 |
S.Sun,
L.Geng,
and
Y.Shamoo
(2006).
Structure and enzymatic properties of a chimeric bacteriophage RB69 DNA polymerase and single-stranded DNA binding protein with increased processivity.
|
| |
Proteins,
65,
231-238.
|
 |
|
PDB codes:
|
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|
 |
S.W.Nelson,
J.Yang,
and
S.J.Benkovic
(2006).
Site-directed mutations of T4 helicase loading protein (gp59) reveal multiple modes of DNA polymerase inhibition and the mechanism of unlocking by gp41 helicase.
|
| |
J Biol Chem,
281,
8697-8706.
|
 |
|
|
|
|
 |
A.Johnson,
and
M.O'Donnell
(2005).
Cellular DNA replicases: components and dynamics at the replication fork.
|
| |
Annu Rev Biochem,
74,
283-315.
|
 |
|
|
|
|
 |
A.T.McGeoch,
and
S.D.Bell
(2005).
Eukaryotic/archaeal primase and MCM proteins encoded in a bacteriophage genome.
|
| |
Cell,
120,
167-168.
|
 |
|
|
|
|
 |
C.Indiani,
P.McInerney,
R.Georgescu,
M.F.Goodman,
and
M.O'Donnell
(2005).
A sliding-clamp toolbelt binds high- and low-fidelity DNA polymerases simultaneously.
|
| |
Mol Cell,
19,
805-815.
|
 |
|
|
|
|
 |
H.Nishida,
S.Ishino,
T.Miyata,
K.Morikawa,
and
Y.Ishino
(2005).
Identification of the critical region in replication factor C from Pyrococcus furiosus for the stable complex formation with proliferating cell nuclear antigen and DNA.
|
| |
Genes Genet Syst,
80,
83-93.
|
 |
|
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|
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PDB code:
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A.Loregian,
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PDB codes:
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F.López de Saro,
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Nature,
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PDB code:
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J.B.Bruning,
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Structural and thermodynamic analysis of human PCNA with peptides derived from DNA polymerase-delta p66 subunit and flap endonuclease-1.
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Structure,
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PDB codes:
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J.K.Kumar,
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PDB codes:
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The bacteriophage T4 late-transcription coactivator gp33 binds the flap domain of Escherichia coli RNA polymerase.
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Cell,
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PDB codes:
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Y.Wang,
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PDB code:
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E.Delagoutte,
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PDB code:
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K.Wong,
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J Biol Chem,
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Intermolecular ion pairs maintain the toroidal structure of Pyrococcus furiosus PCNA.
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Protein Sci,
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PDB codes:
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S.Sun,
and
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Biochemical characterization of interactions between DNA polymerase and single-stranded DNA-binding protein in bacteriophage RB69.
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J Biol Chem,
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J Virol,
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Dissecting the fidelity of bacteriophage RB69 DNA polymerase: site-specific modulation of fidelity by polymerase accessory proteins.
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Genetics,
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J Biol Chem,
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Direct interaction between uracil-DNA glycosylase and a proliferating cell nuclear antigen homolog in the crenarchaeon Pyrobaculum aerophilum.
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J Biol Chem,
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Fidelity of DNA polymerase epsilon holoenzyme from budding yeast Saccharomyces cerevisiae.
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J Biol Chem,
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The processivity factor beta controls DNA polymerase IV traffic during spontaneous mutagenesis and translesion synthesis in vivo.
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EMBO Rep,
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Physical interaction between proliferating cell nuclear antigen and replication factor C from Pyrococcus furiosus.
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Genes Cells,
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PDB code:
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U.Hubscher,
G.Maga,
and
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Eukaryotic DNA polymerases.
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Annu Rev Biochem,
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Protein determinants of RNA binding by DNA polymerase of the T4-related bacteriophage RB69.
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J Biol Chem,
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The influence of the Cdc27 subunit on the properties of the Schizosaccharomyces pombe DNA polymerase delta.
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J Biol Chem,
277,
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W.C.Lam,
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3'-5' exonuclease of Klenow fragment: role of amino acid residues within the single-stranded DNA binding region in exonucleolysis and duplex DNA melting.
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Biochemistry,
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X.Lu,
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Direct interaction of proliferating cell nuclear antigen with the small subunit of DNA polymerase delta.
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J Biol Chem,
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A.Hillisch,
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Recent advances in FRET: distance determination in protein-DNA complexes.
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Curr Opin Struct Biol,
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B.P.Dalrymple,
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A universal protein-protein interaction motif in the eubacterial DNA replication and repair systems.
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Proc Natl Acad Sci U S A,
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D.Jeruzalmi,
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Crystal structure of the processivity clamp loader gamma (gamma) complex of E. coli DNA polymerase III.
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Cell,
106,
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PDB code:
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D.Jeruzalmi,
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Y.Zhao,
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J.Stewart,
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and
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Mechanism of processivity clamp opening by the delta subunit wrench of the clamp loader complex of E. coli DNA polymerase III.
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Cell,
106,
417-428.
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PDB codes:
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G.Mosig,
J.Gewin,
A.Luder,
N.Colowick,
and
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Two recombination-dependent DNA replication pathways of bacteriophage T4, and their roles in mutagenesis and horizontal gene transfer.
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Proc Natl Acad Sci U S A,
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H.E.Kleczkowska,
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hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci.
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Genes Dev,
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J.A.Carrodeguas,
K.Theis,
D.F.Bogenhagen,
and
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(2001).
Crystal structure and deletion analysis show that the accessory subunit of mammalian DNA polymerase gamma, Pol gamma B, functions as a homodimer.
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Mol Cell,
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PDB codes:
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M.A.Trakselis,
M.U.Mayer,
F.T.Ishmael,
R.M.Roccasecca,
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Dynamic protein interactions in the bacteriophage T4 replisome.
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Trends Biochem Sci,
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M.A.Trakselis,
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Creating a dynamic picture of the sliding clamp during T4 DNA polymerase holoenzyme assembly by using fluorescence resonance energy transfer.
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Proc Natl Acad Sci U S A,
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Clamp loader structure predicts the architecture of DNA polymerase III holoenzyme and RFC.
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Curr Biol,
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S.C.Alley,
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Building a replisome solution structure by elucidation of protein-protein interactions in the bacteriophage T4 DNA polymerase holoenzyme.
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J Biol Chem,
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Annu Rev Biochem,
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Crystal structure of an archaeal DNA sliding clamp: proliferating cell nuclear antigen from Pyrococcus furiosus.
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Protein Sci,
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PDB code:
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T.C.Lin,
C.X.Wang,
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and
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3'-5' Exonucleolytic activity of DNA polymerases: structural features that allow kinetic discrimination between ribo- and deoxyribonucleotide residues.
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Biochemistry,
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Opening of the clamp: an intimate view of an ATP-driven biological machine.
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Cell,
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The 3'-->5' exonuclease of DNA polymerase delta can substitute for the 5' flap endonuclease Rad27/Fen1 in processing Okazaki fragments and preventing genome instability.
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Proc Natl Acad Sci U S A,
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The crystal structure of an unusual processivity factor, herpes simplex virus UL42, bound to the C terminus of its cognate polymerase.
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Mol Cell,
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PDB code:
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J.L.Keck,
and
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DNA replication at high resolution.
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Chem Biol,
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Curr Biol,
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Essential interaction between the fission yeast DNA polymerase delta subunit Cdc27 and Pcn1 (PCNA) mediated through a C-terminal p21(Cip1)-like PCNA binding motif.
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EMBO J,
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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
code is
shown on the right.
|
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}
}
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