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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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intracellular
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1 term
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DOI no:
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Cell
123:1213-1226
(2005)
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PubMed id:
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MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks.
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M.Stucki,
J.A.Clapperton,
D.Mohammad,
M.B.Yaffe,
S.J.Smerdon,
S.P.Jackson.
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ABSTRACT
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Histone variant H2AX phosphorylation in response to DNA damage is the major
signal for recruitment of DNA-damage-response proteins to regions of damaged
chromatin. Loss of H2AX causes radiosensitivity, genome instability, and DNA
double-strand-break repair defects, yet the mechanisms underlying these
phenotypes remain obscure. Here, we demonstrate that mammalian MDC1/NFBD1
directly binds to phospho-H2AX (gammaH2AX) by specifically interacting with the
phosphoepitope at the gammaH2AX carboxyl terminus. Moreover, through a
combination of biochemical, cell-biological, and X-ray crystallographic
approaches, we reveal the molecular details of the MDC1/NFBD1-gammaH2AX complex.
These data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is
the major mediator of gammaH2AX recognition following DNA damage. We further
show that MDC1/NFBD1-gammaH2AX complex formation regulates H2AX phosphorylation
and is required for normal radioresistance and efficient accumulation of
DNA-damage-response proteins on damaged chromatin. Thus, binding of MDC1/NFBD1
to gammaH2AX plays a central role in the mammalian response to DNA damage.
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Selected figure(s)
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Figure 1.
Figure 1. MDC1 Interacts Directly with a H2AX
Phosphopeptide via Its BRCT Domains
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Figure 3.
Figure 3. MDC1 Recognition of the H2AX C Terminus
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2005,
123,
1213-1226)
copyright 2005.
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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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PDB code:
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PDB codes:
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PDB code:
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PDB code:
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PDB code:
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Yeast, 24,
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RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly.
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Cell, 131,
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PDB code:
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N.G.Medvedeva,
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Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase.
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Science, 318,
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PDB codes:
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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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