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PDBsum entry 3ei4
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DNA binding protein
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PDB id
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3ei4
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References listed in PDB file
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Key reference
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Title
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Structural basis of uv DNA-Damage recognition by the ddb1-Ddb2 complex.
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Authors
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A.Scrima,
R.Konícková,
B.K.Czyzewski,
Y.Kawasaki,
P.D.Jeffrey,
R.Groisman,
Y.Nakatani,
S.Iwai,
N.P.Pavletich,
N.H.Thomä.
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Ref.
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Cell, 2008,
135,
1213-1223.
[DOI no: ]
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PubMed id
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Abstract
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Ultraviolet (UV) light-induced pyrimidine photodimers are repaired by the
nucleotide excision repair pathway. Photolesions have biophysical parameters
closely resembling undamaged DNA, impeding discovery through damage surveillance
proteins. The DDB1-DDB2 complex serves in the initial detection of UV lesions in
vivo. Here we present the structures of the DDB1-DDB2 complex alone and bound to
DNA containing either a 6-4 pyrimidine-pyrimidone photodimer (6-4PP) lesion or
an abasic site. The structure shows that the lesion is held exclusively by the
WD40 domain of DDB2. A DDB2 hairpin inserts into the minor groove, extrudes the
photodimer into a binding pocket, and kinks the duplex by approximately 40
degrees. The tightly localized probing of the photolesions, combined with
proofreading in the photodimer pocket, enables DDB2 to detect lesions refractory
to detection by other damage surveillance proteins. The structure provides
insights into damage recognition in chromatin and suggests a mechanism by which
the DDB1-associated CUL4 ubiquitin ligase targets proteins surrounding the site
of damage.
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Figure 1.
Figure 1. Overall Structure of the DDB1–DDB2–DNA Complex
(A) Ribbon representation of the DDB[dr]–DNA^6-4PP
complex: DDB2, green; DDB1-BPA, red; DDB1-BPB, magenta;
DDB1-BPC, yellow; DDB1-CTD, gray. The DNA^6-4PP damaged and
undamaged strands are depicted in black and gray, respectively.
(B) Ribbon representation of the DDB[dr]–DNA^6-4PP
complex rotated by 90° about the vertical axis relative to
(A).
(C) Schematic representation of hsDDB1 and drDDB2 with
domain boundaries.
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Figure 3.
Figure 3. Mechanism of 6-4 Photodimer Recognition
(A)
Close-up of the DDB2 hairpin insertion (green) at the lesion
with the damaged and undamaged strands depicted in yellow and
brown, respectively.
(B) Interaction of DDB2 with the
DNA^6-4PP backbone. The backbone of both strands is contacted by
an array of positively charged residues crucial for the
stabilization of the phosphate backbone compression at the
damaged site (D[+1], D[+2]). Parts of the DNA are omitted for
clarity.
(C) Close-up of the photodimer binding pocket
stabilizing the flipped-out dinucleotide. Contacting residues
are shown as stick models in yellow. The pyrimidine ring D[+1]
and the pyrimidone ring D[+2] are shown in black and gray,
respectively. Parts of the DNA have been omitted for clarity.
(D) Chemical structure of the 6-4 pyrimidine-pyrimidone
dimer.
(E) Schematic representation of interactions between
DDB2 and DNA^6-4PP (with colors as in A and B).
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Cell
(2008,
135,
1213-1223)
copyright 2008.
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