1snh: Difference between revisions

Revision as of 16:03, 21 February 2008

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

OverviewOverview

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.

About this StructureAbout this Structure

1SNH is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

ReferenceReference

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., Lee JH, Park CJ, Shin JS, Ikegami T, Akutsu H, Choi BS, Nucleic Acids Res. 2004 Apr 30;32(8):2474-81. Print 2004. PMID:15121904

Page seeded by OCA on Thu Feb 21 15:03:19 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1snh.gif|left|200px]]<br /><applet load="1snh" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1snh.gif|left|200px]]<br /><applet load="1snh" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1snh" />
 '''Solution structure of the DNA Decamer Duplex Containing Double TG Mismatches of Cis-syn Cyclobutane Pyrimidine Dimer'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-SNH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SNH OCA].
+SNH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SNH OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Protein complex]]
 [[Category: Akutsu, H.]]
-[[Category: Choi, B.S.]]
+[[Category: Choi, B S.]]
 [[Category: Ikegami, T.]]
-[[Category: Lee, J.H.]]
+[[Category: Lee, J H.]]
-[[Category: Park, C.J.]]
+[[Category: Park, C J.]]
-[[Category: Shin, J.S.]]
+[[Category: Shin, J S.]]
 [[Category: cpd]]
 [[Category: dna]]
@@ Line 23: / Line 23: @@
 [[Category: major groove widening]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 00:51:27 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:03:19 2008''