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Contents |
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98 a.a.
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79 a.a.
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107 a.a.
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93 a.a.
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84 a.a.
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14 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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X-ray structure of a kaposi's sarcoma herpesvirus lana peptide bound to the nucleosomal core
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Structure:
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Palindromic 146bp human alpha-satellite DNA fragment. Chain: i, j. Engineered: yes. Histone h3. Chain: a, e. Engineered: yes. Histone h4. Chain: b, f. Engineered: yes.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: alpha-satellite DNA. Expressed in: escherichia coli. Expression_system_taxid: 562. Xenopus laevis. African clawed frog. Organism_taxid: 8355.
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Biol. unit:
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Undecamer (from
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Resolution:
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2.90Å
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R-factor:
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0.222
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R-free:
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0.277
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Authors:
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J.V.Chodaparambil,A.J.Barbera,K.M.Kaye,K.Luger
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Key ref:
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A.J.Barbera
et al.
(2006).
The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA.
Science,
311,
856-861.
PubMed id:
DOI:
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Date:
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05-May-05
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Release date:
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28-Feb-06
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PROCHECK
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Headers
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References
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P84233
(H32_XENLA) -
Histone H3.2 from Xenopus laevis
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Seq:
Struc:
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136 a.a.
98 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.
79 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.
107 a.a.*
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P02281
(H2B11_XENLA) -
Histone H2B 1.1 from Xenopus laevis
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Seq:
Struc:
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126 a.a.
93 a.a.
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DOI no:
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Science
311:856-861
(2006)
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PubMed id:
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The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA.
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A.J.Barbera,
J.V.Chodaparambil,
B.Kelley-Clarke,
V.Joukov,
J.C.Walter,
K.Luger,
K.M.Kaye.
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ABSTRACT
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Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear
antigen (LANA) mediates viral genome attachment to mitotic chromosomes. We find
that N-terminal LANA docks onto chromosomes by binding nucleosomes through the
folded region of histones H2A-H2B. The same LANA residues were required for both
H2A-H2B binding and chromosome association. Further, LANA did not bind Xenopus
sperm chromatin, which is deficient in H2A-H2B; chromatin binding was rescued
after assembly of nucleosomes containing H2A-H2B. We also describe the
2.9-angstrom crystal structure of a nucleosome complexed with the first 23 LANA
amino acids. The LANA peptide forms a hairpin that interacts exclusively with an
acidic H2A-H2B region that is implicated in the formation of higher order
chromatin structure. Our findings present a paradigm for how nucleosomes may
serve as binding platforms for viral and cellular proteins and reveal a
previously unknown mechanism for KSHV latency.
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Selected figure(s)
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Figure 1.
Fig. 1. LANA N terminus chromosome binding. (A) LANA scanning
alanine mutants with summaries for chromosome binding, episome
persistence (7), and H2A-H2B binding. nd, not determined. (B)
Metaphase spreads of BJAB cells and BJAB cells stably expressing
LANA, LANA[5]GMR[7], LANA [8]LRS[10], LANA [11]GRS[13], or LANA
[14]TG[15]. Overlay of LANA (green) and chromosomes (red)
generates yellow. Cells containing KSHV episomes are indicated.
Arrows denote LANA [14]TG[15] dots that have detached from
chromosomes. Magnification is 630 x. (C) Metaphase BJAB cells
stably expressing GFP NLS or GFP LANA 1-32 at 630 x
magnification. (D) Proteins co-precipitating with GFP LANA 1-32
(lane 2) were identified after resolution in a 4 to 16% gradient
gel. HC, heavy chain; LC, light chain; asterisk, GFP; &, GFP
LANA 1-32. The stoichiometry of histones within nucleosomes and
their arginine-rich nature contribute to the intense histone
Coomassie staining. Numbers on the left-hand side of the gel are
size markers (kD).
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Figure 4.
Fig. 4. Structure of the LANA-nucleosome complex. (A)
Stereoview of a section of the final 2F[o]-F[c] electron density
map calculated at 2.9 Å and contoured at 2  ,
depicting the LANA peptide. Intramolecular hydrogen bonds are
shown as red dashes. (B) Space-filling representation of the
nucleosome-LANA complex. H2A is shown in yellow, H2B in red, H3
in light blue, H4 in green, and LANA in dark blue. DNA is
silver. (C) Overview of LANA interaction with the H2A-H2B dimer
within the NCP. Only H2A (yellow ribbon), H2B (red ribbon), and
LANA (blue sticks) are shown. Intramolecular and intermolecular
bonds are shown as red and blue dashes, respectively. Secondary
structural elements in the histones are indicated. (D) Crystal
contact between the H4 tail of the neighboring nucleosome and
the H2A-H2B dimer. Orientation and coloring of H2A and H2B is
shown as in (C); the H4 tail is shown in green. (E) LANA
recognizes distinct features of the nucleosomal surface. Charged
surfaces (red, negatively charged; blue, positively charged)
were calculated with GRASP (37). The H2A-H2B dimer (left) and
LANA are shown individually; LANA has been rotated by 90°
along the y axis. The H2A-H2B dimer is in about the same
conformation as in (C). (F) Top view of LANA bound to the
histone dimer within the NCP [rotation by 90° around y and
180° around x with respect to the view in (E)]. Only the
H2A-H2B dimer (charged surface) and LANA (stick model) are
shown.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2006,
311,
856-861)
copyright 2006.
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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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A.Allahverdi,
R.Yang,
N.Korolev,
Y.Fan,
C.A.Davey,
C.F.Liu,
and
L.Nordenskiöld
(2011).
The effects of histone H4 tail acetylations on cation-induced chromatin folding and self-association.
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Nucleic Acids Res,
39,
1680-1691.
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|
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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.
|
|
|
|
|
|
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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.
|
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BMC Struct Biol,
11,
1.
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|
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|
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|
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N.E.Davey,
G.Travé,
and
T.J.Gibson
(2011).
How viruses hijack cell regulation.
|
| |
Trends Biochem Sci,
36,
159-169.
|
|
|
|
|
|
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N.Shimizu
(2011).
Molecular mechanisms of the origin of micronuclei from extrachromosomal elements.
|
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Mutagenesis,
26,
119-123.
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|
|
|
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|
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S.Tan,
and
C.A.Davey
(2011).
Nucleosome structural studies.
|
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Curr Opin Struct Biol,
21,
128-136.
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|
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|
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C.Paulus,
A.Nitzsche,
and
M.Nevels
(2010).
Chromatinisation of herpesvirus genomes.
|
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Rev Med Virol,
20,
34-50.
|
|
|
|
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|
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C.R.Paden,
J.C.Forrest,
N.J.Moorman,
and
S.H.Speck
(2010).
Murine gammaherpesvirus 68 LANA is essential for virus reactivation from splenocytes but not long-term carriage of viral genome.
|
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J Virol,
84,
7214-7224.
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D.Ganem
(2010).
KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine.
|
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J Clin Invest,
120,
939-949.
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G.Sarek,
A.Järviluoma,
H.M.Moore,
S.Tojkander,
S.Vartia,
P.Biberfeld,
M.Laiho,
and
P.M.Ojala
(2010).
Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.
|
| |
PLoS Pathog,
6,
e1000818.
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|
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J.A.West,
and
B.Damania
(2010).
Kaposi's sarcoma-associated herpesvirus and innate immunity.
|
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Future Virol,
5,
185-196.
|
|
|
|
|
|
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J.R.England,
J.Huang,
M.J.Jennings,
R.D.Makde,
and
S.Tan
(2010).
RCC1 uses a conformationally diverse loop region to interact with the nucleosome: a model for the RCC1-nucleosome complex.
|
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J Mol Biol,
398,
518-529.
|
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|
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M.Boulard,
S.Storck,
R.Cong,
R.Pinto,
H.Delage,
and
P.Bouvet
(2010).
Histone variant macroH2A1 deletion in mice causes female-specific steatosis.
|
| |
Epigenetics Chromatin,
3,
8.
|
|
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|
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|
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M.Roupelieva,
S.J.Griffiths,
E.Kremmer,
M.Meisterernst,
A.Viejo-Borbolla,
T.Schulz,
and
J.Haas
(2010).
Kaposi's sarcoma-associated herpesvirus Lana-1 is a major activator of the serum response element and mitogen-activated protein kinase pathways via interactions with the Mediator complex.
|
| |
J Gen Virol,
91,
1138-1149.
|
|
|
|
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|
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M.Thirion,
B.Machiels,
F.Farnir,
G.Donofrio,
L.Gillet,
B.Dewals,
and
A.Vanderplasschen
(2010).
Bovine herpesvirus 4 ORF73 is dispensable for virus growth in vitro, but is essential for virus persistence in vivo.
|
| |
J Gen Virol,
91,
2574-2584.
|
|
|
|
|
|
|
N.Blake
(2010).
Immune evasion by gammaherpesvirus genome maintenance proteins.
|
| |
J Gen Virol,
91,
829-846.
|
|
|
|
|
|
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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.
|
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PDB code:
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|
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S.H.Speck,
and
D.Ganem
(2010).
Viral latency and its regulation: lessons from the gamma-herpesviruses.
|
| |
Cell Host Microbe,
8,
100-115.
|
|
|
|
|
|
|
S.J.Han,
J.Hu,
B.Pierce,
Z.Weng,
and
R.Renne
(2010).
Mutational analysis of the latency-associated nuclear antigen DNA-binding domain of Kaposi's sarcoma-associated herpesvirus reveals structural conservation among gammaherpesvirus origin-binding proteins.
|
| |
J Gen Virol,
91,
2203-2215.
|
|
|
|
|
|
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S.Matsumura,
L.M.Persson,
L.Wong,
and
A.C.Wilson
(2010).
The latency-associated nuclear antigen interacts with MeCP2 and nucleosomes through separate domains.
|
| |
J Virol,
84,
2318-2330.
|
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|
|
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|
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V.Sekhar,
S.C.Reed,
and
A.A.McBride
(2010).
Interaction of the betapapillomavirus E2 tethering protein with mitotic chromosomes.
|
| |
J Virol,
84,
543-557.
|
|
|
|
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|
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W.Chen,
I.B.Hilton,
M.R.Staudt,
C.E.Burd,
and
D.P.Dittmer
(2010).
Distinct p53, p53:LANA, and LANA complexes in Kaposi's Sarcoma--associated Herpesvirus Lymphomas.
|
| |
J Virol,
84,
3898-3908.
|
|
|
|
|
|
|
A.M.Meehan,
D.T.Saenz,
J.H.Morrison,
J.A.Garcia-Rivera,
M.Peretz,
M.Llano,
and
E.M.Poeschla
(2009).
LEDGF/p75 proteins with alternative chromatin tethers are functional HIV-1 cofactors.
|
| |
PLoS Pathog,
5,
e1000522.
|
|
|
|
|
|
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B.Kelley-Clarke,
E.De Leon-Vazquez,
K.Slain,
A.J.Barbera,
and
K.M.Kaye
(2009).
Role of Kaposi's sarcoma-associated herpesvirus C-terminal LANA chromosome binding in episome persistence.
|
| |
J Virol,
83,
4326-4337.
|
|
|
|
|
|
|
C.Aresté,
and
D.J.Blackbourn
(2009).
Modulation of the immune system by Kaposi's sarcoma-associated herpesvirus.
|
| |
Trends Microbiol,
17,
119-129.
|
|
|
|
|
|
|
G.Haraldsen,
J.Balogh,
J.Pollheimer,
J.Sponheim,
and
A.M.Küchler
(2009).
Interleukin-33 - cytokine of dual function or novel alarmin?
|
| |
Trends Immunol,
30,
227-233.
|
|
|
|
|
|
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H.Cui,
S.K.Ghosh,
and
M.Jayaram
(2009).
The selfish yeast plasmid uses the nuclear motor Kip1p but not Cin8p for its localization and equal segregation.
|
| |
J Cell Biol,
185,
251-264.
|
|
|
|
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|
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J.Gao,
J.M.Coulson,
A.Whitehouse,
and
N.Blake
(2009).
Reduction in RNA levels rather than retardation of translation is responsible for the inhibition of major histocompatibility complex class I antigen presentation by the glutamic acid-rich repeat of herpesvirus saimiri open reading frame 73.
|
| |
J Virol,
83,
273-282.
|
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|
|
|
|
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J.Hu,
E.Liu,
and
R.Renne
(2009).
Involvement of SSRP1 in latent replication of Kaposi's sarcoma-associated herpesvirus.
|
| |
J Virol,
83,
11051-11063.
|
|
|
|
|
|
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K.M.Feeney,
and
J.L.Parish
(2009).
Targeting mitotic chromosomes: a conserved mechanism to ensure viral genome persistence.
|
| |
Proc Biol Sci,
276,
1535-1544.
|
|
|
|
|
|
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K.W.Wen,
D.P.Dittmer,
and
B.Damania
(2009).
Disruption of LANA in rhesus rhadinovirus generates a highly lytic recombinant virus.
|
| |
J Virol,
83,
9786-9802.
|
|
|
|
|
|
|
M.Ottinger,
D.Pliquet,
T.Christalla,
R.Frank,
J.P.Stewart,
and
T.F.Schulz
(2009).
The interaction of the gammaherpesvirus 68 orf73 protein with cellular BET proteins affects the activation of cell cycle promoters.
|
| |
J Virol,
83,
4423-4434.
|
|
|
|
|
|
|
M.Sakamoto,
S.Noguchi,
S.Kawashima,
Y.Okada,
T.Enomoto,
M.Seki,
and
M.Horikoshi
(2009).
Global analysis of mutual interaction surfaces of nucleosomes with comprehensive point mutants.
|
| |
Genes Cells,
14,
1271-1330.
|
|
|
|
|
|
|
S.B.Kutluay,
and
S.J.Triezenberg
(2009).
Role of chromatin during herpesvirus infections.
|
| |
Biochim Biophys Acta,
1790,
456-466.
|
|
|
|
|
|
|
Y.Yang,
A.P.Lyubartsev,
N.Korolev,
and
L.Nordenskiöld
(2009).
Computer modeling reveals that modifications of the histone tail charges define salt-dependent interaction of the nucleosome core particles.
|
| |
Biophys J,
96,
2082-2094.
|
|
|
|
|
|
|
A.Lin,
S.Wang,
T.Nguyen,
K.Shire,
and
L.Frappier
(2008).
The EBNA1 protein of Epstein-Barr virus functionally interacts with Brd4.
|
| |
J Virol,
82,
12009-12019.
|
|
|
|
|
|
|
C.R.Clapier,
S.Chakravarthy,
C.Petosa,
C.Fernández-Tornero,
K.Luger,
and
C.W.Müller
(2008).
Structure of the Drosophila nucleosome core particle highlights evolutionary constraints on the H2A-H2B histone dimer.
|
| |
Proteins,
71,
1-7.
|
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PDB code:
|
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|
|
|
|
|
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J.Tobaly-Tapiero,
P.Bittoun,
J.Lehmann-Che,
O.Delelis,
M.L.Giron,
H.de Thé,
and
A.Saïb
(2008).
Chromatin tethering of incoming foamy virus by the structural Gag protein.
|
| |
Traffic,
9,
1717-1727.
|
|
|
|
|
|
|
L.Roussel,
M.Erard,
C.Cayrol,
and
J.P.Girard
(2008).
Molecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocket.
|
| |
EMBO Rep,
9,
1006-1012.
|
|
|
|
|
|
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P.M.Lieberman
(2008).
Chromatin organization and virus gene expression.
|
| |
J Cell Physiol,
216,
295-302.
|
|
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|
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|
|
R.Griffiths,
S.M.Harrison,
S.Macnab,
and
A.Whitehouse
(2008).
Mapping the minimal regions within the ORF73 protein required for herpesvirus saimiri episomal persistence.
|
| |
J Gen Virol,
89,
2843-2850.
|
|
|
|
|
|
|
S.J.McBryant,
C.Krause,
C.L.Woodcock,
and
J.C.Hansen
(2008).
The silent information regulator 3 protein, SIR3p, binds to chromatin fibers and assembles a hypercondensed chromatin architecture in the presence of salt.
|
| |
Mol Cell Biol,
28,
3563-3572.
|
|
|
|
|
|
|
Z.Zhou,
H.Feng,
D.F.Hansen,
H.Kato,
E.Luk,
D.I.Freedberg,
L.E.Kay,
C.Wu,
and
Y.Bai
(2008).
NMR structure of chaperone Chz1 complexed with histones H2A.Z-H2B.
|
| |
Nat Struct Mol Biol,
15,
868-869.
|
|
|
PDB code:
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|
|
|
|
|
|
B.Kelley-Clarke,
M.E.Ballestas,
V.Srinivasan,
A.J.Barbera,
T.Komatsu,
T.A.Harris,
M.Kazanjian,
and
K.M.Kaye
(2007).
Determination of Kaposi's sarcoma-associated herpesvirus C-terminal latency-associated nuclear antigen residues mediating chromosome association and DNA binding.
|
| |
J Virol,
81,
4348-4356.
|
|
|
|
|
|
|
C.E.Petre,
S.H.Sin,
and
D.P.Dittmer
(2007).
Functional p53 signaling in Kaposi's sarcoma-associated herpesvirus lymphomas: implications for therapy.
|
| |
J Virol,
81,
1912-1922.
|
|
|
|
|
|
|
D.J.Tremethick
(2007).
Higher-order structures of chromatin: the elusive 30 nm fiber.
|
| |
Cell,
128,
651-654.
|
|
|
|
|
|
|
H.J.Kwun,
S.R.da Silva,
I.M.Shah,
N.Blake,
P.S.Moore,
and
Y.Chang
(2007).
Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mimics Epstein-Barr virus EBNA1 immune evasion through central repeat domain effects on protein processing.
|
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J Virol,
81,
8225-8235.
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I.Neeli,
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Divergent members of a single autoreactive B cell clone retain specificity for apoptotic blebs.
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Mol Immunol,
44,
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J.Liu,
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G.Liao,
and
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The Kaposi's sarcoma-associated herpesvirus LANA protein stabilizes and activates c-Myc.
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J Virol,
81,
10451-10459.
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J.Liu,
H.Martin,
M.Shamay,
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and
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(2007).
Kaposi's sarcoma-associated herpesvirus LANA protein downregulates nuclear glycogen synthase kinase 3 activity and consequently blocks differentiation.
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J Virol,
81,
4722-4731.
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J.V.Chodaparambil,
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and
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A charged and contoured surface on the nucleosome regulates chromatin compaction.
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Nat Struct Mol Biol,
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K.Matsubara,
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Global analysis of functional surfaces of core histones with comprehensive point mutants.
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Genes Cells,
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K.Noguchi,
H.Fukazawa,
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Gamma-herpesviruses and cellular signaling in AIDS-associated malignancies.
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Cancer Sci,
98,
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M.Fujimuro,
S.D.Hayward,
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(2007).
Molecular piracy: manipulation of the ubiquitin system by Kaposi's sarcoma-associated herpesvirus.
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Rev Med Virol,
17,
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R.Griffiths,
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Herpesvirus saimiri episomal persistence is maintained via interaction between open reading frame 73 and the cellular chromosome-associated protein MeCP2.
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J Virol,
81,
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R.L.Skalsky,
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Analysis of viral cis elements conferring Kaposi's sarcoma-associated herpesvirus episome partitioning and maintenance.
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J Virol,
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S.C.Verma,
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An autonomous replicating element within the KSHV genome.
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Cell Host Microbe,
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S.C.Verma,
T.Choudhuri,
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The minimal replicator element of the Kaposi's sarcoma-associated herpesvirus terminal repeat supports replication in a semiconservative and cell-cycle-dependent manner.
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J Virol,
81,
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T.L.Caterino,
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Chromatin structure depends on what's in the nucleosome's pocket.
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Nat Struct Mol Biol,
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Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association.
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Mol Cell,
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PDB code:
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F.Lu,
L.Day,
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and
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Acetylation of the latency-associated nuclear antigen regulates repression of Kaposi's sarcoma-associated herpesvirus lytic transcription.
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J Virol,
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J.L.Parish,
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ChlR1 is required for loading papillomavirus E2 onto mitotic chromosomes and viral genome maintenance.
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Mol Cell,
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J.You,
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Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes.
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J Virol,
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L.A.Adang,
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Asynchronous progression through the lytic cascade and variations in intracellular viral loads revealed by high-throughput single-cell analysis of Kaposi's sarcoma-associated herpesvirus infection.
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J Virol,
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M.Fujimuro
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[Kaposi's sarcoma-associated herpesvirus and mechanisms of oncogenesis]
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Uirusu,
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M.Ottinger,
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Kaposi's sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3-induced G1 cell cycle arrest.
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J Virol,
80,
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M.Shamay,
A.Krithivas,
J.Zhang,
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(2006).
Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi's sarcoma-associated herpesvirus LANA.
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Proc Natl Acad Sci U S A,
103,
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S.C.Verma,
B.G.Bajaj,
Q.Cai,
H.Si,
T.Seelhammer,
and
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(2006).
Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus recruits uracil DNA glycosylase 2 at the terminal repeats and is important for latent persistence of the virus.
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J Virol,
80,
11178-11190.
|
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The most recent references are shown first.
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only a partial list as not all journals are covered by
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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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