In vivo deamination of cytosine-containing cyclobutane pyrimidine dimers in E. coli: a feasible part of UV-mutagenesis

Burger, A.; Fix, Douglas F.; Liu, H.; Hays, John B.; Bockrath, Richard

doi:10.1016/s0027-5107(02)00310-x

Cited by 34 publications

(19 citation statements)

References 45 publications

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“…That is, the deamination of cytosine produces a uracil-containing CPD, which frequently induces C-to-T transitions after Pol -dependent error-free synthesis (58), although uracil residues and uracil/guanine mispairs are preferentially removed by the base excision repair and mismatch repair pathways, respectively. The in vivo deamination of cytosines in CPDs takes from several hours to a few days, depending on local sequence context (2,7,33,50,59,62). Taking these results together, it is likely that cytosine residues in dermal CPDs are more likely to be deaminated than those in epidermal CPDs, since these lesions persist longer in the dermis than in the epidermis, as mentioned above.…”

Section: Role For Pol In Prevention Of Uv-induced Mesenchymal Tumorsmentioning

confidence: 95%

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

Ohkumo

Kondo

Yokoi

et al. 2006

Molecular and Cellular Biology

106

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DNA polymerase(Pol ) is the product of the Polh gene, which is responsible for the group variant of xeroderma pigmentosum, a rare inherited recessive disease which is characterized by susceptibility to sunlightinduced skin cancer. We recently reported in a study of Polh mutant mice that Pol is involved in the somatic hypermutation of immunoglobulin genes, but the cancer predisposition of Polh ؊/؊ mice has not been examined until very recently. Another translesion synthesis polymerase, Pol , a Pol paralog encoded by the Poli gene, is naturally deficient in the 129 mouse strain, and the function of Pol is enigmatic. Here, we generated Polh Poli doubledeficient mice and compared the tumor susceptibility of them with Polh-or Poli-deficient animals under the same genetic background. While Pol deficiency does not influence the UV sensitivity of mouse fibroblasts irrespective of Polh genotype, Polh Poli double-deficient mice show slightly earlier onset of skin tumor formation. Intriguingly, histological diagnosis after chronic treatment with UV light reveals that Pol deficiency leads to the formation of mesenchymal tumors, such as sarcomas, that are not observed in Polh ؊/؊ mice. These results suggest the involvement of the Pol and Pol proteins in UV-induced skin carcinogenesis.

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Section: Role For Pol In Prevention Of Uv-induced Mesenchymal Tumorsmentioning

confidence: 95%

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

Ohkumo

Kondo

Yokoi

et al. 2006

Molecular and Cellular Biology

106

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“…It has been shown that UVB enhances the formation of CPDs at methylated CpG sites [Drouin and Therrien, 1997], whereas CpG sites become refractory to 64PP formation when methylated [Glickman et al, 1986;Pfeifer et al, 1991]. CPD formation is known to promote deamination of cytosine residues in the dimer [Tessman et al, 1994;Barak et al, 1995;Tu et al, 1998;Burger et al, 2003], converting a cytosine-containing CPD to a uracilor thymine-containing CPD, which could cause C ? T mutations through translesional DNA synthesis (TLS) with DNA polymerase h [Jiang and Taylor, 1993;Johnson Either base adjacent to the 5 0 or 3 0 side of the cytosine that should be subject to mutation to thymine is shown.…”

Section: Uvb-induced Mutation Spectrummentioning

confidence: 99%

Mutation spectrum in UVB-exposed skin epidermis of a mildly-affectedXpg-deficient mouse

Wang¹,

Saito²,

Shiomi³

et al. 2006

Environ. Mol. Mutagen.

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A C-terminal 183 amino acid-truncated mutation of the mouse Xpg gene (XpgDeltaex15) gives rise to a partial deficiency in nucleotide excision repair in homozygously affected cells. We studied the effect of this mutation on UVB-induced mutagenesis in mouse skin, using transgenic mice harboring lambda-phage-based bacterial lacZ genes as a mutational reporter. UVB increased the lacZ mutant frequency in the epidermis moderately in the homozygous mutant mice, but significantly higher than in the wild-type or the heterozygous mice, whereas background mutant frequencies were not appreciably different among the three mouse genotypes. Ninety-eight lacZ mutant sequences isolated from the UVB-exposed epidermis of the XpgDeltaex15-homozygous mice were analyzed and compared with mutant sequences from the wild-type mice. The spectra of the mutations in the two mouse genotypes were not significantly different, and they were highly UV-specific. There were frequent C --> T transitions at dipyrimidine sites and several CC --> TT tandem mutations, although the UV-specific mutations occurred more frequently at CpG sites in the mutant mice. The distribution of the mutations observed in the lacZ transgene and the preferred sequence context of the UV-specific C --> T mutations (5'-TC-3' > 5'-CC-3' > 5'-CT-3') in the Xpg-mutant mice were similar to those found in the wild-type mice. Despite these similarities, we detected a previously unrecognized type of the UV-induced mutation only in the Xpg mutant (6/98 in the mutation spectrum of the mutant vs. 0/76 in the wild-type; P = 0.035), which is characterized by multiple base substitutions or frameshifts within a three-nucleotide sequence containing a dipyrimidine. We propose that this putative new class of mutation, which we refer to as a "triplet mutation", is characteristic of UV-induced mutation in an excision-repair-deficient background.

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“…Because C-containing CPDs must deaminate to become mutagenic by the polymerase pathway, factors that accelerate deamination are also expected to enhance C to T mutation frequency. Although much is known about the deamination of CPDs in vitro and in vivo (2,(5)(6)(7)(8)(9)(10)(11)(12)(13), nothing is known about the effect of chromatin structure on their deamination in vivo and how this may relate to UV mutation hot spots and cold spots. Nucleosomes are the main structural component of chromatin and are composed of about 147 base pairs of DNA wrapped 1.65 times around a histone core (14 -16).…”

mentioning

confidence: 99%

Rapid Deamination of Cyclobutane Pyrimidine Dimer Photoproducts at TCG Sites in a Translationally and Rotationally Positioned Nucleosome in Vivo

Cannistraro

Pondugula

Song

et al. 2015

Journal of Biological Chemistry

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Background: DNA photoproduct deamination contributes to mutations. Results: Cyclobutane pyrimidine dimers (CPDs) deaminate fastest at TCG sites, and the rate depends on the position of the CPD in a nucleosome determined from hydroxyl radical footprinting. Conclusion: Deamination could explain the high C to T mutation rate at TCG sites, which can be further modulated by nucleosomes. Significance: Sequence context and chromatin structure can modulate UV mutagenesis.

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In vivo deamination of cytosine-containing cyclobutane pyrimidine dimers in E. coli: a feasible part of UV-mutagenesis

Cited by 34 publications

References 45 publications

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase η and Mesenchymal Tumors in Mice Deficient for DNA Polymerase ι

Mutation spectrum in UVB-exposed skin epidermis of a mildly-affectedXpg-deficient mouse

Rapid Deamination of Cyclobutane Pyrimidine Dimer Photoproducts at TCG Sites in a Translationally and Rotationally Positioned Nucleosome in Vivo

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