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99 a.a.
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80 a.a.
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105 a.a.
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93 a.a.
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93 a.a.
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* Residue conservation analysis
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PDB id:
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Structural protein/DNA
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Title:
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Ligand binding alters the structure and dynamics of nucleosomal DNA
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Structure:
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Palindromic 146 base pair DNA fragment. Chain: i, j. Engineered: yes. Histone h3.3c. Chain: a, e. Engineered: yes. Histone h4. Chain: b, f. Engineered: yes.
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Source:
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Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Xenopus laevis. African clawed frog. Organism_taxid: 8355. Gene: h3-5. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Biol. unit:
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Undecamer (from
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Resolution:
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2.65Å
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R-factor:
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0.223
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R-free:
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0.267
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Authors:
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R.K.Suto,R.S.Edayathumangalam,C.L.White,C.Melander,J.M.Gottesfeld, P.B.Dervan,K.Luger
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Key ref:
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R.K.Suto
et al.
(2003).
Crystal structures of nucleosome core particles in complex with minor groove DNA-binding ligands.
J Mol Biol,
326,
371-380.
PubMed id:
DOI:
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Date:
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18-Jun-02
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Release date:
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18-Feb-03
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PROCHECK
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Headers
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References
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P02302
(H3C_XENLA) -
Histone H3.3C from Xenopus laevis
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Seq:
Struc:
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136 a.a.
99 a.a.*
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P62799
(H4_XENLA) -
Histone H4 from Xenopus laevis
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Seq:
Struc:
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103 a.a.
80 a.a.
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P06897
(H2A1_XENLA) -
Histone H2A type 1 from Xenopus laevis
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Seq:
Struc:
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130 a.a.
105 a.a.*
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Enzyme class:
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Chains A, B, C, D, E, F, G, H:
E.C.?
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DOI no:
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J Mol Biol
326:371-380
(2003)
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PubMed id:
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Crystal structures of nucleosome core particles in complex with minor groove DNA-binding ligands.
|
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R.K.Suto,
R.S.Edayathumangalam,
C.L.White,
C.Melander,
J.M.Gottesfeld,
P.B.Dervan,
K.Luger.
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ABSTRACT
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We determined the crystal structures of three nucleosome core particles in
complex with site-specific DNA-binding ligands, the pyrrole-imidazole
polyamides. While the structure of the histone octamer and its interaction with
the DNA remain unaffected by ligand binding, nucleosomal DNA undergoes
significant structural changes at the ligand-binding sites and in adjacent
regions to accommodate the ligands. Our findings suggest that twist diffusion
occurs over long distances through tightly bound nucleosomal DNA. This may be
relevant to the mechanism of ATP-dependent and spontaneous nucleosome
translocation, and to the effect of bound factors on nucleosome dynamics.
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Selected figure(s)
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Figure 2.
Figure 2. DNA parameters. (a) Minor groove widths
were averaged for the 10 -- 11 base-pairs between indi-
vidual protein -- DNA contact points, and are plotted
against the superhelix location. Values for X-NCP,
NCP-PA1, NCP-PA2, and NCP-PA3 are plotted against
SHLs in black, blue, green, and magenta, respectively.
The location of polyamides in each structure is indicated
by blue, green, and magenta boxes, respectively. Data
points for SHLs at which stretching occurs are circled;
the equivalent regions in the long half are indicated by
broken-line circles. (b) DNA twist angles, averaged as
in (a). The position of stretch sites is indicated as in (a).
A vertical line indicates the location of the dyad axis
(SHL 0).
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Figure 4.
Figure 4. Stretching of nucleosomal DNA. (a) A schematic describing the alignment procedure. Long (turquoise) and
short DNA halves (black and brown, respectively for NCP-PA1,2 and X-NCP) were aligned using LSQMAN (Uppsala
Software Factory). Base-pair 73 is indicated by F. Stretching of the short half occurs at SHL-5 in NCP-PA1 and 2, and at
SHL-2 in X-NCP. Hatched regions indicate those regions of the short half where the sequence is out of register by one
base-pair compared to the long half. (b) Overview of parts of the structure of NCP-PA1, viewed down the superhelical
axis as in Figure 1(a). Only base-pairs 13 -- 78 (short half) and associated proteins are shown. The long half (turquoise,
base-pairs 68 -- 134) was superimposed onto the short half (white) as described for (a). Polyamide 1 is shown in blue;
histone coloring is as described for Figure 1. The dyad axis is indicated by a broken line, base-pair 73 is indicated by
F, the L1L2 DNA-binding motif is indicated by O, the a1 -- a1 motif is indicated by *. (c) X-NCP with aligned long
and short halves (turquoise and gold, respectively) was superimposed onto NCP-PA1 by a structural alignment of 30
base-pairs centered on either stretching site, as shown in (a). All other labels are as in (b).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2003,
326,
371-380)
copyright 2003.
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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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F.Mueller-Planitz,
H.Klinker,
J.Ludwigsen,
and
P.B.Becker
(2013).
The ATPase domain of ISWI is an autonomous nucleosome remodeling machine.
|
| |
Nat Struct Mol Biol,
20,
82-89.
|
|
|
|
|
|
|
K.Luger,
M.L.Dechassa,
and
D.J.Tremethick
(2012).
New insights into nucleosome and chromatin structure: an ordered state or a disordered affair?
|
| |
Nat Rev Mol Cell Biol,
13,
436-447.
|
|
|
|
|
|
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A.J.Andrews,
and
K.Luger
(2011).
Nucleosome structure(s) and stability: variations on a theme.
|
| |
Annu Rev Biophys,
40,
99.
|
|
|
|
|
|
|
A.Marathe,
and
M.Bansal
(2011).
An ensemble of B-DNA dinucleotide geometries lead to characteristic nucleosomal DNA structure and provide plasticity required for gene expression.
|
| |
BMC Struct Biol,
11,
1.
|
|
|
|
|
|
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S.Tan,
and
C.A.Davey
(2011).
Nucleosome structural studies.
|
| |
Curr Opin Struct Biol,
21,
128-136.
|
|
|
|
|
|
|
B.Heddi,
C.Oguey,
C.Lavelle,
N.Foloppe,
and
B.Hartmann
(2010).
Intrinsic flexibility of B-DNA: the experimental TRX scale.
|
| |
Nucleic Acids Res,
38,
1034-1047.
|
|
|
|
|
|
|
C.D.Carlson,
C.L.Warren,
K.E.Hauschild,
M.S.Ozers,
N.Qadir,
D.Bhimsaria,
Y.Lee,
F.Cerrina,
and
A.Z.Ansari
(2010).
Specificity landscapes of DNA binding molecules elucidate biological function.
|
| |
Proc Natl Acad Sci U S A,
107,
4544-4549.
|
|
|
|
|
|
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D.M.Chenoweth,
and
P.B.Dervan
(2010).
Structural basis for cyclic Py-Im polyamide allosteric inhibition of nuclear receptor binding.
|
| |
J Am Chem Soc,
132,
14521-14529.
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PDB code:
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F.Xu,
A.V.Colasanti,
Y.Li,
and
W.K.Olson
(2010).
Long-range effects of histone point mutations on DNA remodeling revealed from computational analyses of SIN-mutant nucleosome structures.
|
| |
Nucleic Acids Res,
38,
6872-6882.
|
|
|
|
|
|
|
G.D.Bowman
(2010).
Mechanisms of ATP-dependent nucleosome sliding.
|
| |
Curr Opin Struct Biol,
20,
73-81.
|
|
|
|
|
|
|
G.E.Davey,
B.Wu,
Y.Dong,
U.Surana,
and
C.A.Davey
(2010).
DNA stretching in the nucleosome facilitates alkylation by an intercalating antitumour agent.
|
| |
Nucleic Acids Res,
38,
2081-2088.
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|
PDB code:
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H.Yue,
Y.Zhu,
Y.Wang,
and
G.Chen
(2010).
Investigation and improvement of DNA cleavage models of polyamide + Cu(II) nuclease + OOH- ligands bound to DNA.
|
| |
BMC Struct Biol,
10,
35.
|
|
|
|
|
|
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K.Mohideen,
R.Muhammad,
and
C.A.Davey
(2010).
Perturbations in nucleosome structure from heavy metal association.
|
| |
Nucleic Acids Res,
38,
6301-6311.
|
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|
PDB codes:
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R.D.Makde,
J.R.England,
H.P.Yennawar,
and
S.Tan
(2010).
Structure of RCC1 chromatin factor bound to the nucleosome core particle.
|
| |
Nature,
467,
562-566.
|
|
|
PDB code:
|
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|
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|
|
S.Watanabe,
M.Resch,
W.Lilyestrom,
N.Clark,
J.C.Hansen,
C.Peterson,
and
K.Luger
(2010).
Structural characterization of H3K56Q nucleosomes and nucleosomal arrays.
|
| |
Biochim Biophys Acta,
1799,
480-486.
|
|
|
PDB codes:
|
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|
|
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|
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T.Moreno,
J.Pous,
J.A.Subirana,
and
J.L.Campos
(2010).
Coiled-coil conformation of a pentamidine-DNA complex.
|
| |
Acta Crystallogr D Biol Crystallogr,
66,
251-257.
|
|
|
PDB code:
|
|
|
|
|
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|
|
D.M.Chenoweth,
and
P.B.Dervan
(2009).
Allosteric modulation of DNA by small molecules.
|
| |
Proc Natl Acad Sci U S A,
106,
13175-13179.
|
|
|
PDB codes:
|
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|
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|
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R.C.Todd,
and
S.J.Lippard
(2009).
Inhibition of transcription by platinum antitumor compounds.
|
| |
Metallomics,
1,
280-291.
|
|
|
|
|
|
|
S.Balasubramanian,
F.Xu,
and
W.K.Olson
(2009).
DNA sequence-directed organization of chromatin: structure-based computational analysis of nucleosome-binding sequences.
|
| |
Biophys J,
96,
2245-2260.
|
|
|
|
|
|
|
S.Kundu,
and
C.L.Peterson
(2009).
Role of chromatin states in transcriptional memory.
|
| |
Biochim Biophys Acta,
1790,
445-455.
|
|
|
|
|
|
|
B.Wu,
and
C.A.Davey
(2008).
Platinum drug adduct formation in the nucleosome core alters nucleosome mobility but not positioning.
|
| |
Chem Biol,
15,
1023-1028.
|
|
|
|
|
|
|
D.Svozil,
J.Kalina,
M.Omelka,
and
B.Schneider
(2008).
DNA conformations and their sequence preferences.
|
| |
Nucleic Acids Res,
36,
3690-3706.
|
|
|
|
|
|
|
G.E.Davey,
and
C.A.Davey
(2008).
Chromatin - a new, old drug target?
|
| |
Chem Biol Drug Des,
72,
165-170.
|
|
|
|
|
|
|
S.Keleş,
C.L.Warren,
C.D.Carlson,
and
A.Z.Ansari
(2008).
CSI-Tree: a regression tree approach for modeling binding properties of DNA-binding molecules based on cognate site identification (CSI) data.
|
| |
Nucleic Acids Res,
36,
3171-3184.
|
|
|
|
|
|
|
T.C.Bishop
(2008).
Geometry of the nucleosomal DNA superhelix.
|
| |
Biophys J,
95,
1007-1017.
|
|
|
|
|
|
|
D.Roccatano,
A.Barthel,
and
M.Zacharias
(2007).
Structural flexibility of the nucleosome core particle at atomic resolution studied by molecular dynamics simulation.
|
| |
Biopolymers,
85,
407-421.
|
|
|
|
|
|
|
M.J.Hannon
(2007).
Supramolecular DNA recognition.
|
| |
Chem Soc Rev,
36,
280-295.
|
|
|
|
|
|
|
N.G.Nickols,
C.S.Jacobs,
M.E.Farkas,
and
P.B.Dervan
(2007).
Improved nuclear localization of DNA-binding polyamides.
|
| |
Nucleic Acids Res,
35,
363-370.
|
|
|
|
|
|
|
A.Saha,
J.Wittmeyer,
and
B.R.Cairns
(2006).
Chromatin remodelling: the industrial revolution of DNA around histones.
|
| |
Nat Rev Mol Cell Biol,
7,
437-447.
|
|
|
|
|
|
|
C.E.Caesar,
R.Johnsson,
U.Ellervik,
K.R.Fox,
P.Lincoln,
and
B.Nordén
(2006).
A polarized-light spectroscopy study of interactions of a hairpin polyamide with DNA.
|
| |
Biophys J,
91,
904-911.
|
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|
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J.D.Trzupek,
J.M.Gottesfeld,
and
D.L.Boger
(2006).
Alkylation of duplex DNA in nucleosome core particles by duocarmycin SA and yatakemycin.
|
| |
Nat Chem Biol,
2,
79-82.
|
|
|
|
|
|
|
K.S.Gates
(2006).
Getting under wraps: alkylating DNA in the nucleosome.
|
| |
Nat Chem Biol,
2,
64-66.
|
|
|
|
|
|
|
B.Liu,
P.Yu,
P.G.Alluri,
and
T.Kodadek
(2005).
Simple reporter gene-based assays for hairpin poly(amide) conjugate permeability and DNA-binding activity in living cells.
|
| |
Mol Biosyst,
1,
307-317.
|
|
|
|
|
|
|
S.Chakravarthy,
S.K.Gundimella,
C.Caron,
P.Y.Perche,
J.R.Pehrson,
S.Khochbin,
and
K.Luger
(2005).
Structural characterization of the histone variant macroH2A.
|
| |
Mol Cell Biol,
25,
7616-7624.
|
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PDB codes:
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|
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W.Ge,
B.Schneider,
and
W.K.Olson
(2005).
Knowledge-based elastic potentials for docking drugs or proteins with nucleic acids.
|
| |
Biophys J,
88,
1166-1190.
|
|
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|
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|
|
A.Flaus,
and
T.Owen-Hughes
(2004).
Mechanisms for ATP-dependent chromatin remodelling: farewell to the tuna-can octamer?
|
| |
Curr Opin Genet Dev,
14,
165-173.
|
|
|
|
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|
|
B.Z.Olenyuk,
G.J.Zhang,
J.M.Klco,
N.G.Nickols,
W.G.Kaelin,
and
P.B.Dervan
(2004).
Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist.
|
| |
Proc Natl Acad Sci U S A,
101,
16768-16773.
|
|
|
|
|
|
|
M.S.Murty,
and
H.Sugiyama
(2004).
Biology of N-methylpyrrole-N-methylimidazole hairpin polyamide.
|
| |
Biol Pharm Bull,
27,
468-474.
|
|
|
|
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|
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P.Auffinger,
L.Bielecki,
and
E.Westhof
(2004).
Anion binding to nucleic acids.
|
| |
Structure,
12,
379-388.
|
|
|
|
|
|
|
R.S.Edayathumangalam,
P.Weyermann,
J.M.Gottesfeld,
P.B.Dervan,
and
K.Luger
(2004).
Molecular recognition of the nucleosomal "supergroove".
|
| |
Proc Natl Acad Sci U S A,
101,
6864-6869.
|
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PDB code:
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|
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|
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S.Chakravarthy,
Y.Bao,
V.A.Roberts,
D.Tremethick,
and
K.Luger
(2004).
Structural characterization of histone H2A variants.
|
| |
Cold Spring Harb Symp Quant Biol,
69,
227-234.
|
|
|
|
|
|
|
U.M.Muthurajan,
Y.Bao,
L.J.Forsberg,
R.S.Edayathumangalam,
P.N.Dyer,
C.L.White,
and
K.Luger
(2004).
Crystal structures of histone Sin mutant nucleosomes reveal altered protein-DNA interactions.
|
| |
EMBO J,
23,
260-271.
|
|
|
PDB codes:
|
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|
|
B.Dudouet,
R.Burnett,
L.A.Dickinson,
M.R.Wood,
C.Melander,
J.M.Belitsky,
B.Edelson,
N.Wurtz,
C.Briehn,
P.B.Dervan,
and
J.M.Gottesfeld
(2003).
Accessibility of nuclear chromatin by DNA binding polyamides.
|
| |
Chem Biol,
10,
859-867.
|
|
|
|
|
|
|
K.Luger
(2003).
Structure and dynamic behavior of nucleosomes.
|
| |
Curr Opin Genet Dev,
13,
127-135.
|
|
|
|
|
|
|
P.B.Dervan,
and
B.S.Edelson
(2003).
Recognition of the DNA minor groove by pyrrole-imidazole polyamides.
|
| |
Curr Opin Struct Biol,
13,
284-299.
|
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|
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|
|
S.Aoyagi,
P.A.Wade,
and
J.J.Hayes
(2003).
Nucleosome sliding induced by the xMi-2 complex does not occur exclusively via a simple twist-diffusion mechanism.
|
| |
J Biol Chem,
278,
30562-30568.
|
|
|
|
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|
|
S.W.Ebbinghaus
(2003).
Site-selective DNA binding drugs.
|
| |
Chem Biol,
10,
895-897.
|
|
|
|
|
|
|
T.G.Uil,
H.J.Haisma,
and
M.G.Rots
(2003).
Therapeutic modulation of endogenous gene function by agents with designed DNA-sequence specificities.
|
| |
Nucleic Acids Res,
31,
6064-6078.
|
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|
|
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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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| |
Links
