NDLI: NMR structure of the DNA decamer duplex containing double T·G mismatches of cis–syn cyclobutane pyrimidine dimer: implications for DNA damage recognition by the XPC

Content Provider	PubMed Central
Author	Lee, Joon-hwa Park, Chin-ju Shin, Jae-sun Ikegami, Takahisa Akutsu, Hideo Choi, Byong-seok
Copyright Year	2004
Abstract	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.
Related Links	http://dx.doi.org/10.1093/nar/gkh568
Ending Page	2481
Page Count	8
Starting Page	2474
File Format	PDF
ISSN	13624962
e-ISSN	13624962
Journal	Nucleic Acids Research
Issue Number	8
Volume Number	32
Language	English
Publisher	Oxford University Press
Publisher Date	2004-04-28
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics

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NMR structure of the DNA decamer duplex containing double T·G mismatches of cis–syn cyclobutane pyrimidine dimer: implications for DNA damage recognition by the XPC–hHR23B complex

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NMR structure of the DNA decamer duplex containing double T·G mismatches of cis–syn cyclobutane pyrimidine dimer: implications for DNA damage recognition by the XPC–hHR23B complex

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