1SNH

Solution structure of the DNA Decamer Duplex Containing Double TG Mismatches of Cis-syn Cyclobutane Pyrimidine Dimer

Summary for 1SNH

• Entry DOI: 10.2210/pdb1snh/pdb
• Related: 1pib
• Descriptor: 5'-D(*CP*GP*CP*AP*TP*TP*AP*CP*GP*C)-3', 5'-D(*GP*CP*GP*TP*GP*GP*TP*GP*CP*G)-3' (2 entities in total)
• Functional Keywords: dna, g-t mismatch, cpd, major groove widening
• Total number of polymer chains: 2
• Total formula weight: 6122.01

Authors

Lee, J.H.,Park, C.J.,Shin, J.S.,Ikegami, T.,Akutsu, H.,Choi, B.S. (deposition date: 2004-03-11, release date: 2004-05-18, Last modification date: 2024-05-29)

Primary citation

Lee, J.H.,Park, C.J.,Shin, J.S.,Ikegami, T.,Akutsu, H.,Choi, B.S.
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.
Nucleic Acids Res., 32:2474-2481, 2004

PubMed 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.

PubMed: 15121904
DOI: 10.1093/nar/gkh568

Experimental method

SOLUTION NMR