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PDBsum entry 1jeq
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DNA binding protein
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PDB id
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1jeq
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure of the ku heterodimer bound to DNA and its implications for double-Strand break repair.
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Authors
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J.R.Walker,
R.A.Corpina,
J.Goldberg.
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Ref.
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Nature, 2001,
412,
607-614.
[DOI no: ]
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PubMed id
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Abstract
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The Ku heterodimer (Ku70 and Ku80 subunits) contributes to genomic integrity
through its ability to bind DNA double-strand breaks and facilitate repair by
the non-homologous end-joining pathway. The crystal structure of the human Ku
heterodimer was determined both alone and bound to a 55-nucleotide DNA element
at 2.7 and 2.5 A resolution, respectively. Ku70 and Ku80 share a common topology
and form a dyad-symmetrical molecule with a preformed ring that encircles duplex
DNA. The binding site can cradle two full turns of DNA while encircling only the
central 3-4 base pairs (bp). Ku makes no contacts with DNA bases and few with
the sugar-phosphate backbone, but it fits sterically to major and minor groove
contours so as to position the DNA helix in a defined path through the protein
ring. These features seem well designed to structurally support broken DNA ends
and to bring the DNA helix into phase across the junction during end processing
and ligation.
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Figure 2.
Figure 2: Structure of the Ku-DNA complex. a, View down the
DNA helix. Ku70 is coloured red and Ku80 orange. Only the 14-bp
duplex portion of DNA is shown; the sugar-phosphate backbone is
coloured light grey and the bases dark grey. b, Side view. Black
line indicates the molecular dyad axis. Terminal base pairs are
numbered +8 (broken DNA end) and -6. c, Abbreviated topology
diagram showing the fold of Ku70 and Ku80. Green rods indicate
 -helices;
blue arrows indicate  -strands.
d, Stereo difference electron density map viewed down the
molecular dyad axis (white symbol). Blue contour lines show
electron density at the 2.4  -level
in a |F[o]| - |F[c]| (2.5 Å resolution) map calculated after
simulated-annealing refinement of a model lacking nucleotides
from levels -2 to +6 of the 34-residue oligonucleotide.
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Figure 4.
Figure 4: Surface depictions of Ku. a, Space-filling model
showing Ku bound to DNA. The model was prepared by fitting a
32-bp B DNA to the crystallographically observed duplex. DNA
extends towards the viewer to the +11 level. Ku70 is coloured
red and Ku80 orange. DNA is shown with one light grey and one
dark grey strand. b, Molecular surface representation of Ku is
coloured according to electrostatic potential, calculated using
the program GRASP44. Negative potential is coloured red and
positive potential blue.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2001,
412,
607-614)
copyright 2001.
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