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PDBsum entry 4yir
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DNA binding protein/DNA
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PDB id
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4yir
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References listed in PDB file
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Key reference
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Title
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Kinetic gating mechanism of DNA damage recognition by rad4/xpc.
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Authors
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X.Chen,
Y.Velmurugu,
G.Zheng,
B.Park,
Y.Shim,
Y.Kim,
L.Liu,
B.Van houten,
C.He,
A.Ansari,
J.H.Min.
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Ref.
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Nat Commun, 2015,
6,
5849.
[DOI no: ]
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PubMed id
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Abstract
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The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair
by recognizing DNA lesions before recruiting downstream factors. How XPC detects
structurally diverse lesions embedded within normal DNA is unknown. Here we
present a crystal structure that captures the yeast XPC orthologue (Rad4) on a
single register of undamaged DNA. The structure shows that a disulphide-tethered
Rad4 flips out normal nucleotides and adopts a conformation similar to that seen
with damaged DNA. Contrary to many DNA repair enzymes that can directly reject
non-target sites as structural misfits, our results suggest that Rad4/XPC uses a
kinetic gating mechanism whereby lesion selectivity arises from the kinetic
competition between DNA opening and the residence time of Rad4/XPC per site.
This mechanism is further supported by measurements of Rad4-induced
lesion-opening times using temperature-jump perturbation spectroscopy. Kinetic
gating may be a general mechanism used by site-specific DNA-binding proteins to
minimize time-consuming interrogations of non-target sites.
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