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PDBsum entry 1snh
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References listed in PDB file
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Key reference
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Title
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Nmr structure of the DNA decamer duplex containing double tG mismatches of cis-Syn cyclobutane pyrimidine dimer: implications for DNA damage recognition by the xpc-Hhr23b complex.
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Authors
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J.H.Lee,
C.J.Park,
J.S.Shin,
T.Ikegami,
H.Akutsu,
B.S.Choi.
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Ref.
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Nucleic Acids Res, 2004,
32,
2474-2481.
[DOI no: ]
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PubMed id
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Abstract
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The cis-syn cyclobutane pyrimidine dimer (CPD) is a cytotoxic, mutagenic and
carcinogenic DNA photoproduct and is repaired by the nucleotide excision repair
(NER) pathway in mammalian cells. The XPC-hHR23B complex as the initiator of
global genomic NER binds to sites of certain kinds of DNA damage. Although CPDs
are rarely recognized by the XPC-hHR23B complex, the presence of mismatched
bases opposite a CPD significantly increased the binding affinity of the
XPC-hHR23B complex to the CPD. In order to decipher the properties of the DNA
structures that determine the binding affinity for XPC-hHR23B to DNA, we carried
out structural analyses of the various types of CPDs by NMR spectroscopy. The
DNA duplex which contains a single 3' T*G wobble pair in a CPD (CPD/GA duplex)
induces little conformational distortion. However, severe distortion of the
helical conformation occurs when a CPD contains double T*G wobble pairs (CPD/GG
duplex) even though the T residues of the CPD form stable hydrogen bonds with
the opposite G residues. The helical bending angle of the CPD/GG duplex was
larger than those of the CPD/GA duplex and properly matched CPD/AA duplex. The
fluctuation of the backbone conformation and significant changes in the widths
of the major and minor grooves at the double T*G wobble paired site were also
observed in the CPD/GG duplex. These structural features were also found in a
duplex that contains the (6-4) adduct, which is efficiently recognized by the
XPC-hHR23B complex. Thus, we suggest that the unique structural features of the
DNA double helix (that is, helical bending, flexible backbone conformation, and
significant changes of the major and/or minor grooves) might be important
factors in determining the binding affinity of the XPC-hHR23B complex to DNA.
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Headers
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