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* Residue conservation analysis
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Enzyme class:
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Chains A, B:
E.C.?
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DOI no:
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Nat Struct Mol Biol
13:360-364
(2006)
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PubMed id:
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Structural basis for DNA recognition and processing by UvrB.
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J.J.Truglio,
E.Karakas,
B.Rhau,
H.Wang,
M.J.DellaVecchia,
B.Van Houten,
C.Kisker.
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ABSTRACT
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DNA-damage recognition in the nucleotide excision repair (NER) cascade is a
complex process, operating on a wide variety of damages. UvrB is the central
component in prokaryotic NER, directly involved in DNA-damage recognition and
guiding the DNA through repair synthesis. We report the first structure of a
UvrB-double-stranded DNA complex, providing insights into the mechanism by which
UvrB binds DNA, leading to formation of the preincision complex. One DNA strand,
containing a 3' overhang, threads behind a beta-hairpin motif of UvrB,
indicating that this motif inserts between the strands of the double helix,
thereby locking down either the damaged or undamaged strand. The nucleotide
directly behind the beta-hairpin is flipped out and inserted into a small,
highly conserved pocket in UvrB.
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Selected figure(s)
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Figure 1.
Figure 1. The UvrBâDNA complex and selected electron density.
(a) Surface of UvrB is color-coded by domain (yellow, 1a;
green, 1b; blue, 2; red, 3; cyan, the -hairpin
of UvrB; magenta, the newly formed -sheet
after DNA binding). DNA is illustrated by spokes and letters,
color-coded by nucleotide type. The letter representation of the
DNA is in a similar orientation to the DNA in the structure.
Black letters, disordered nucleotides; F, fluorescein-adducted
thymine. The fluorescein-dT, although partially ordered (Fig.
1b), has been omitted from the figure for clarity. (b) 2F[o] -
F[c] electron density map contoured at 1.0 covering
the DNA. Gray, carbons of unmodified nucleotides; green, carbons
of partially ordered fluorescein; magenta, electron density for
the fluorescein. Nucleotides are labeled consecutively from 5'
to 3', omitting numbers of disordered residues. (c) UvrBâDNA
model showing how the inner strand of the DNA (red) travels
between the -hairpin
(cyan) and domain 1b and the outer strand (green) travels around
the outside of the -hairpin.
(d) Superposition of DNA-bound and apo UvrB. -hairpin
regions of the DNA-bound (cyan and blue) and apo UvrB (PDB entry
1D9X; yellow and gold) are superimposed. Select residues are
shown with color-coded labeling. Dark gray spokes represent the
bound DNA and the surface of the remainder of the UvrBâDNA
complex is shown in gray.
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Figure 2.
Figure 2. Interactions between UvrB and the DNA. (a) UvrB
bound to DNA. Gray surface, UvrB; cyan ribbon, -hairpin;
yellow, outer DNA strand; green, inner DNA strand. Selected
residues from UvrB are indicated. 3' and 5' ends of the DNA are
labeled in red. Nucleotides are numbered sequentially starting
from the 5' end and omitting numbers corresponding to
nucleotides in the loop region. (b,c) Views rotated 45°
(b) and 90°
(c) from a along the vertical axis.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2006,
13,
360-364)
copyright 2006.
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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.Pakotiprapha,
M.Samuels,
K.Shen,
J.H.Hu,
and
D.Jeruzalmi
(2012).
Structure and mechanism of the UvrA-UvrB DNA damage sensor.
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Nat Struct Mol Biol,
19,
291-298.
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PDB codes:
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M.Jaciuk,
E.Nowak,
K.Skowronek,
A.TaĆska,
and
M.Nowotny
(2011).
Structure of UvrA nucleotide excision repair protein in complex with modified DNA.
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Nat Struct Mol Biol,
18,
191-197.
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PDB code:
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N.Mazloum,
M.A.Stegman,
D.L.Croteau,
B.Van Houten,
N.S.Kwon,
Y.Ling,
C.Dickinson,
A.Venugopal,
M.A.Towheed,
and
C.Nathan
(2011).
Identification of a chemical that inhibits the mycobacterial UvrABC complex in nucleotide excision repair.
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Biochemistry,
50,
1329-1335.
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K.Isozaki,
and
K.Miki
(2010).
Design, synthesis, and complementary recognition of beta-hairpin peptides stabilized by artificial DNA base-pairing amino acids.
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Chem Commun (Camb),
46,
2947-2949.
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L.Manelyte,
Y.I.Kim,
A.J.Smith,
R.M.Smith,
and
N.J.Savery
(2010).
Regulation and rate enhancement during transcription-coupled DNA repair.
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Mol Cell,
40,
714-724.
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N.M.Kad,
H.Wang,
G.G.Kennedy,
D.M.Warshaw,
and
B.Van Houten
(2010).
Collaborative dynamic DNA scanning by nucleotide excision repair proteins investigated by single- molecule imaging of quantum-dot-labeled proteins.
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Mol Cell,
37,
702-713.
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D.Pakotiprapha,
Y.Liu,
G.L.Verdine,
and
D.Jeruzalmi
(2009).
A Structural Model for the Damage-sensing Complex in Bacterial Nucleotide Excision Repair.
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J Biol Chem,
284,
12837-12844.
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PDB code:
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H.Wang,
M.Lu,
M.S.Tang,
B.Van Houten,
J.B.Ross,
M.Weinfeld,
and
X.C.Le
(2009).
DNA wrapping is required for DNA damage recognition in the Escherichia coli DNA nucleotide excision repair pathway.
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Proc Natl Acad Sci U S A,
106,
12849-12854.
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J.Atkinson,
C.P.Guy,
C.J.Cadman,
G.F.Moolenaar,
N.Goosen,
and
P.McGlynn
(2009).
Stimulation of UvrD helicase by UvrAB.
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J Biol Chem,
284,
9612-9623.
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K.Wagner,
G.Moolenaar,
J.van Noort,
and
N.Goosen
(2009).
Single-molecule analysis reveals two separate DNA-binding domains in the Escherichia coli UvrA dimer.
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Nucleic Acids Res,
37,
1962-1972.
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L.Jia,
K.Kropachev,
S.Ding,
B.Van Houten,
N.E.Geacintov,
and
S.Broyde
(2009).
Exploring damage recognition models in prokaryotic nucleotide excision repair with a benzo[a]pyrene-derived lesion in UvrB.
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Biochemistry,
48,
8948-8957.
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L.Manelyte,
C.P.Guy,
R.M.Smith,
M.S.Dillingham,
P.McGlynn,
and
N.J.Savery
(2009).
The unstructured C-terminal extension of UvrD interacts with UvrB, but is dispensable for nucleotide excision repair.
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DNA Repair (Amst),
8,
1300-1310.
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D.L.Croteau,
M.J.DellaVecchia,
L.Perera,
and
B.Van Houten
(2008).
Cooperative damage recognition by UvrA and UvrB: identification of UvrA residues that mediate DNA binding.
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DNA Repair (Amst),
7,
392-404.
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D.Pakotiprapha,
Y.Inuzuka,
B.R.Bowman,
G.F.Moolenaar,
N.Goosen,
D.Jeruzalmi,
and
G.L.Verdine
(2008).
Crystal structure of Bacillus stearothermophilus UvrA provides insight into ATP-modulated dimerization, UvrB interaction, and DNA binding.
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Mol Cell,
29,
122-133.
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PDB code:
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E.J.Enemark,
and
L.Joshua-Tor
(2008).
On helicases and other motor proteins.
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Curr Opin Struct Biol,
18,
243-257.
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L.A.Christensen,
H.Wang,
B.Van Houten,
and
K.M.Vasquez
(2008).
Efficient processing of TFO-directed psoralen DNA interstrand crosslinks by the UvrABC nuclease.
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Nucleic Acids Res,
36,
7136-7145.
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S.C.Shuck,
E.A.Short,
and
J.J.Turchi
(2008).
Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology.
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Cell Res,
18,
64-72.
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S.C.Wolski,
J.Kuper,
P.Hänzelmann,
J.J.Truglio,
D.L.Croteau,
B.Van Houten,
and
C.Kisker
(2008).
Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD.
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PLoS Biol,
6,
e149.
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PDB code:
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W.Yang
(2008).
Structure and mechanism for DNA lesion recognition.
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Cell Res,
18,
184-197.
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E.Karakas,
J.J.Truglio,
D.Croteau,
B.Rhau,
L.Wang,
B.Van Houten,
and
C.Kisker
(2007).
Structure of the C-terminal half of UvrC reveals an RNase H endonuclease domain with an Argonaute-like catalytic triad.
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EMBO J,
26,
613-622.
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PDB codes:
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M.J.DellaVecchia,
W.K.Merritt,
Y.Peng,
T.W.Kirby,
E.F.DeRose,
G.A.Mueller,
B.Van Houten,
and
R.E.London
(2007).
NMR analysis of [methyl-13C]methionine UvrB from Bacillus caldotenax reveals UvrB-domain 4 heterodimer formation in solution.
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J Mol Biol,
373,
282-295.
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N.J.Savery
(2007).
The molecular mechanism of transcription-coupled DNA repair.
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Trends Microbiol,
15,
326-333.
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O.Maillard,
U.Camenisch,
F.C.Clement,
K.B.Blagoev,
and
H.Naegeli
(2007).
DNA repair triggered by sensors of helical dynamics.
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Trends Biochem Sci,
32,
494-499.
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S.Karamanou,
G.Gouridis,
E.Papanikou,
G.Sianidis,
I.Gelis,
D.Keramisanou,
E.Vrontou,
C.G.Kalodimos,
and
A.Economou
(2007).
Preprotein-controlled catalysis in the helicase motor of SecA.
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EMBO J,
26,
2904-2914.
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H.Wang,
M.J.DellaVecchia,
M.Skorvaga,
D.L.Croteau,
D.A.Erie,
and
B.Van Houten
(2006).
UvrB domain 4, an autoinhibitory gate for regulation of DNA binding and ATPase activity.
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J Biol Chem,
281,
15227-15237.
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J.Rudolf,
V.Makrantoni,
W.J.Ingledew,
M.J.Stark,
and
M.F.White
(2006).
The DNA repair helicases XPD and FancJ have essential iron-sulfur domains.
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Mol Cell,
23,
801-808.
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K.Theis
(2006).
One-way traffic control in replication termination.
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Nat Chem Biol,
2,
455-456.
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R.Gupta,
S.Sharma,
K.M.Doherty,
J.A.Sommers,
S.B.Cantor,
and
R.M.Brosh
(2006).
Inhibition of BACH1 (FANCJ) helicase by backbone discontinuity is overcome by increased motor ATPase or length of loading strand.
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Nucleic Acids Res,
34,
6673-6683.
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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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