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PDBsum entry 3ii6
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Ligase/DNA binding protein
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PDB id
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3ii6
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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 and functional interaction between the human DNA repair proteins DNA ligase IV and xrcc4.
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Authors
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P.Y.Wu,
P.Frit,
S.Meesala,
S.Dauvillier,
M.Modesti,
S.N.Andres,
Y.Huang,
J.Sekiguchi,
P.Calsou,
B.Salles,
M.S.Junop.
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Ref.
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Mol Cell Biol, 2009,
29,
3163-3172.
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PubMed id
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Abstract
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Nonhomologous end-joining represents the major pathway used by human cells to
repair DNA double-strand breaks. It relies on the XRCC4/DNA ligase IV complex to
reseal DNA strands. Here we report the high-resolution crystal structure of
human XRCC4 bound to the carboxy-terminal tandem BRCT repeat of DNA ligase IV.
The structure differs from the homologous Saccharomyces cerevisiae complex and
reveals an extensive DNA ligase IV binding interface formed by a
helix-loop-helix structure within the inter-BRCT linker region, as well as
significant interactions involving the second BRCT domain, which induces a kink
in the tail region of XRCC4. We further demonstrate that interaction with the
second BRCT domain of DNA ligase IV is necessary for stable binding to XRCC4 in
cells, as well as to achieve efficient dominant-negative effects resulting in
radiosensitization after ectopic overexpression of DNA ligase IV fragments in
human fibroblasts. Together our findings provide unanticipated insight for
understanding the physical and functional architecture of the nonhomologous
end-joining ligation complex.
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