Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2011 Feb 25;2868:6329-35. doi: 10.1074/jbc.M110.183178.
Show Gene links
Show Anatomy links
Rotational position of a 5-methylcytosine-containing cyclobutane pyrimidine dimer in a nucleosome greatly affects its deamination rate.
Song Q, Cannistraro VJ, Taylor JS.
???displayArticle.abstract???
C to T mutation hotspots in skin cancers occur primarily at methylated CpG sites that coincide with sites of UV-induced cyclobutane pyrimidine dimer (CPD) formation. These mutations are proposed to arise from the insertion of A by DNA polymerase η opposite the T that results from deamination of the methylC ((m)C) within the CPD. Although the frequency of CPD formation and repair is modestly modulated by its rotational position within a nucleosome, the effect of position on the rate of (m)C deamination in a CPD has not been previously studied. We now report that deamination of a T(m)C CPD whose sugar phosphate backbone is positioned against the histone core surface decreases by a factor of 4.7, whereas that of a T(m)C CPD positioned away from the surface increases by a factor of 8.9 when compared with unbound DNA. Because the (m)Cs undergoing deamination are in similar steric environments, the difference in rate appears to be a consequence of a difference in the flexibility and compression of the two sites due to DNA bending. Considering that formation of the CPD positioned away from the surface is also enhanced by a factor of two, a T(m)CG site in this position might be expected to have up to an 84-fold higher probability of resulting in a UV-induced (m)C to T mutation than one positioned against the surface. These results indicate that rotational position may play an important role in the formation of UV-induced C to T mutation hotspots, as well as in the mutagenic mechanism of other DNA lesions.
Balasubramanian,
DNA strand breaking by the hydroxyl radical is governed by the accessible surface areas of the hydrogen atoms of the DNA backbone.
1998, Pubmed
Balasubramanian,
DNA strand breaking by the hydroxyl radical is governed by the accessible surface areas of the hydrogen atoms of the DNA backbone.
1998,
Pubmed Becker,
Origin of ultraviolet damage in DNA.
1989,
Pubmed Brash,
A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma.
1991,
Pubmed Cadet,
Ultraviolet radiation-mediated damage to cellular DNA.
2005,
Pubmed Cannistraro,
Methyl CpG binding protein 2 (MeCP2) enhances photodimer formation at methyl-CpG sites but suppresses dimer deamination.
2010,
Pubmed Cannistraro,
Acceleration of 5-methylcytosine deamination in cyclobutane dimers by G and its implications for UV-induced C-to-T mutation hotspots.
2009,
Pubmed Carpenter,
Sequence-dependent enhancement of hydrolytic deamination of cytosines in DNA by the restriction enzyme PspGI.
2006,
Pubmed Celewicz,
The photochemistry of thymidylyl-(3'-5')-5-methyl-2'-deoxycytidine in aqueous solution.
2005,
Pubmed Davey,
Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution.
2002,
Pubmed
,
Xenbase Douki,
Individual determination of the yield of the main UV-induced dimeric pyrimidine photoproducts in DNA suggests a high mutagenicity of CC photolesions.
2001,
Pubmed Douki,
Formation of cyclobutane dimers and (6-4) photoproducts upon far-UV photolysis of 5-methylcytosine-containing dinucleotide monophosphates.
1994,
Pubmed Drouin,
UVB-induced cyclobutane pyrimidine dimer frequency correlates with skin cancer mutational hotspots in p53.
1997,
Pubmed Fix,
Thermal resistance to photoreactivation of specific mutations potentiated in E. coli B/r ung by ultraviolet light.
1981,
Pubmed Frederico,
A sensitive genetic assay for the detection of cytosine deamination: determination of rate constants and the activation energy.
1990,
Pubmed Gale,
UV-induced formation of pyrimidine dimers in nucleosome core DNA is strongly modulated with a period of 10.3 bases.
1987,
Pubmed Giglia-Mari,
TP53 mutations in human skin cancers.
2003,
Pubmed Hara,
Effect of damage type on stimulation of human excision nuclease by SWI/SNF chromatin remodeling factor.
2003,
Pubmed Jiang,
In vivo evidence that UV-induced C-->T mutations at dipyrimidine sites could result from the replicative bypass of cis-syn cyclobutane dimers or their deamination products.
1993,
Pubmed Jing,
Thermodynamic and base-pairing studies of matched and mismatched DNA dodecamer duplexes containing cis-syn, (6-4) and Dewar photoproducts of TT.
1998,
Pubmed Kosmoski,
Synthesis and nucleosome structure of DNA containing a UV photoproduct at a specific site.
1999,
Pubmed Kosmoski,
DNA repair of a single UV photoproduct in a designed nucleosome.
2001,
Pubmed
,
Xenbase Kreutzer,
Oxidized, deaminated cytosines are a source of C --> T transitions in vivo.
1998,
Pubmed Lee,
Deamination of 5-methylcytosines within cyclobutane pyrimidine dimers is an important component of UVB mutagenesis.
2003,
Pubmed Lemaire,
Kinetic analysis of the deamination reactions of cyclobutane dimers of thymidylyl-3',5'-2'-deoxycytidine and 2'-deoxycytidylyl-3',5'-thymidine.
1993,
Pubmed Li,
Accessibility of a glucocorticoid response element in a nucleosome depends on its rotational positioning.
1995,
Pubmed Li,
Translational positioning of a nucleosomal glucocorticoid response element modulates glucocorticoid receptor affinity.
1993,
Pubmed Liu,
Nucleotide excision repair of the 5 S ribosomal RNA gene assembled into a nucleosome.
2000,
Pubmed
,
Xenbase Luger,
Dynamic nucleosomes.
2006,
Pubmed Luger,
Crystal structure of the nucleosome core particle at 2.8 A resolution.
1997,
Pubmed McCulloch,
Preferential cis-syn thymine dimer bypass by DNA polymerase eta occurs with biased fidelity.
2004,
Pubmed Mu,
Recognition and repair of compound DNA lesions (base damage and mismatch) by human mismatch repair and excision repair systems.
1997,
Pubmed Ober,
Cisplatin damage overrides the predefined rotational setting of positioned nucleosomes.
2007,
Pubmed Park,
Crystal structure of a DNA decamer containing a cis-syn thymine dimer.
2002,
Pubmed Pehrson,
Effects of DNA looping on pyrimidine dimer formation.
1992,
Pubmed Pehrson,
Thymine dimer formation as a probe of the path of DNA in and between nucleosomes in intact chromatin.
1989,
Pubmed Pfeifer,
Mutations induced by ultraviolet light.
2005,
Pubmed Pfeifer,
Formation and processing of UV photoproducts: effects of DNA sequence and chromatin environment.
1997,
Pubmed Setlow,
Cyclobutane-type pyrimidine dimers in polynucleotides.
1966,
Pubmed Shen,
The rate of hydrolytic deamination of 5-methylcytosine in double-stranded DNA.
1994,
Pubmed Sohail,
Protection of DNA by alpha/beta-type small, acid-soluble proteins from Bacillus subtilis spores against cytosine deamination.
2002,
Pubmed Sugasawa,
A multistep damage recognition mechanism for global genomic nucleotide excision repair.
2001,
Pubmed Suquet,
UV damage to DNA strongly influences its rotational setting on the histone surface of reconstituted nucleosomes.
1993,
Pubmed Svedruzić,
Accommodation and repair of a UV photoproduct in DNA at different rotational settings on the nucleosome surface.
2005,
Pubmed
,
Xenbase Taylor,
cis-syn thymine dimers are not absolute blocks to replication by DNA polymerase I of Escherichia coli in vitro.
1990,
Pubmed Thoma,
Repair of UV lesions in nucleosomes--intrinsic properties and remodeling.
2005,
Pubmed Tommasi,
Sunlight induces pyrimidine dimers preferentially at 5-methylcytosine bases.
1997,
Pubmed Tu,
Sequence and time-dependent deamination of cytosine bases in UVB-induced cyclobutane pyrimidine dimers in vivo.
1998,
Pubmed Vu,
DNA synthesis past a 5-methylC-containing cis-syn-cyclobutane pyrimidine dimer by yeast pol eta is highly nonmutagenic.
2006,
Pubmed Wang,
Nucleotide excision repair of DNA by human cell extracts is suppressed in reconstituted nucleosomes.
1991,
Pubmed
,
Xenbase Washington,
Accuracy of thymine-thymine dimer bypass by Saccharomyces cerevisiae DNA polymerase eta.
2000,
Pubmed Yoon,
The DNA damage spectrum produced by simulated sunlight.
2000,
Pubmed You,
Involvement of 5-methylcytosine in sunlight-induced mutagenesis.
1999,
Pubmed You,
Cyclobutane pyrimidine dimers are responsible for the vast majority of mutations induced by UVB irradiation in mammalian cells.
2001,
Pubmed You,
Similarities in sunlight-induced mutational spectra of CpG-methylated transgenes and the p53 gene in skin cancer point to an important role of 5-methylcytosine residues in solar UV mutagenesis.
2001,
Pubmed You,
Cyclobutane pyrimidine dimers form preferentially at the major p53 mutational hotspot in UVB-induced mouse skin tumors.
2000,
Pubmed Yu,
Requirement of DNA polymerase eta for error-free bypass of UV-induced CC and TC photoproducts.
2001,
Pubmed Ziegler,
Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers.
1993,
Pubmed