In VivoSpectrum of UVC-induced Mutation in Mouse Skin Epidermis May Reflect the Cytosine Deamination Propensity of Cyclobutane Pyrimidine Dimers

2015 ◽  
Vol 91 (6) ◽  
pp. 1488-1496 ◽  
Author(s):  
Hironobu Ikehata ◽  
Toshio Mori ◽  
Masayuki Yamamoto
Keyword(s):  
Mouse Skin ◽  
Cyclobutane Pyrimidine Dimers ◽  
Cytosine Deamination ◽  
Induced Mutation ◽  
Pyrimidine Dimers ◽  
Skin Epidermis

scholarly journals The major mechanism of melanoma mutations is based on deamination of cytosine in pyrimidine dimers as determined by circle damage sequencing

2021 ◽  
Vol 7 (31) ◽  
pp. eabi6508
Author(s):  
Seung-Gi Jin ◽  
Dean Pettinga ◽  
Jennifer Johnson ◽  
Peipei Li ◽  
Gerd P. Pfeifer
Keyword(s):  
Sequence Specificity ◽  
Uvb Radiation ◽  
Cyclobutane Pyrimidine Dimers ◽  
Sequence Context ◽  
Cytosine Deamination ◽  
Transcription Start Sites ◽  
Major Mechanism ◽  
Pyrimidine Dimers ◽  
Genome Wide

Sunlight-associated melanomas carry a unique C-to-T mutation signature. UVB radiation induces cyclobutane pyrimidine dimers (CPDs) as the major form of DNA damage, but the mechanism of how CPDs cause mutations is unclear. To map CPDs at single-base resolution genome wide, we developed the circle damage sequencing (circle-damage-seq) method. In human cells, CPDs form preferentially in a tetranucleotide sequence context (5′-Py-T<>Py-T/A), but this alone does not explain the tumor mutation patterns. To test whether mutations arise at CPDs by cytosine deamination, we specifically mapped UVB-induced cytosine-deaminated CPDs. Transcription start sites (TSSs) were protected from CPDs and deaminated CPDs, but both lesions were enriched immediately upstream of the TSS, suggesting a mutation-promoting role of bound transcription factors. Most importantly, the genomic dinucleotide and trinucleotide sequence specificity of deaminated CPDs matched the prominent mutation signature of melanomas. Our data identify the cytosine-deaminated CPD as the leading premutagenic lesion responsible for mutations in melanomas.

scholarly journals Quantitative analysis of UV photolesions suggests that cyclobutane pyrimidine dimers produced in mouse skin by UVB are more mutagenic than those produced by UVC

2018 ◽  
Vol 17 (4) ◽  
pp. 404-413 ◽  
Author(s):  
Hironobu Ikehata ◽  
Toshio Mori ◽  
Thierry Douki ◽  
Jean Cadet ◽  
Masayuki Yamamoto
Keyword(s):  
Quantitative Analysis ◽  
Transgenic Mice ◽  
Mouse Skin ◽  
Cyclobutane Pyrimidine Dimers ◽  
Pyrimidine Dimers ◽  
Mutation Assay

The quantification of UV photolesions with a calibrated ELISA and the mutation assay with transgenic mice revealed that the molecular genotoxicity of CPDs depends on UVR components and skin tissues.

Wavelength‐ and Tissue‐dependent Variations in the Mutagenicity of Cyclobutane Pyrimidine Dimers in Mouse Skin

2019 ◽  
Vol 96 (1) ◽  
pp. 94-104 ◽  
Author(s):  
Hironobu Ikehata ◽  
Toshio Mori ◽  
Yasuhiro Kamei ◽  
Thierry Douki ◽  
Jean Cadet ◽  
...  
Keyword(s):  
Mouse Skin ◽  
Cyclobutane Pyrimidine Dimers ◽  
Pyrimidine Dimers

scholarly journals UVA1 Genotoxicity Is Mediated Not by Oxidative Damage but by Cyclobutane Pyrimidine Dimers in Normal Mouse Skin

2008 ◽  
Vol 128 (9) ◽  
pp. 2289-2296 ◽  
Author(s):  
Hironobu Ikehata ◽  
Kazuaki Kawai ◽  
Jun-ichiro Komura ◽  
Ko Sakatsume ◽  
Liangcheng Wang ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Normal Mouse ◽  
Mouse Skin ◽  
Cyclobutane Pyrimidine Dimers ◽  
Pyrimidine Dimers

scholarly journals Repurposing INCI-registered compounds as skin prebiotics for probiotic Staphylococcus epidermidis against UV-B

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Arun Balasubramaniam ◽  
Prakoso Adi ◽  
Do Thi Tra My ◽  
Sunita Keshari ◽  
Raman Sankar ◽  
...  
Keyword(s):  
Bacterial Species ◽  
Protective Action ◽  
Mouse Skin ◽  
Short Chain Fatty Acids ◽  
Skin Lesions ◽  
Ultraviolet B ◽  
Cyclobutane Pyrimidine Dimers ◽  
Pyrimidine Dimers ◽  
Cosmetic Ingredients ◽  
Genes Encoding

AbstractRepurposing existing compounds for new indications may facilitate the discovery of skin prebiotics which have not been well defined. Four compounds that have been registered by the International Nomenclature of Cosmetic Ingredients (INCI) were included to study their abilities to induce the fermentation of Staphylococcusepidermidis (S. epidermidis), a bacterial species abundant in the human skin. Liquid coco-caprylate/caprate (LCC), originally used as an emollient, effectively initiated the fermentation of S. epidermidis ATCC 12228, produced short-chain fatty acids (SCFAs), and provoked robust electricity. Application of LCC plus electrogenic S. epidermidis ATCC 12228 on mouse skin significantly reduced ultraviolet B (UV-B)-induced injuries which were evaluated by the formation of 4-hydroxynonenal (4-HNE), cyclobutane pyrimidine dimers (CPD), and skin lesions. A S. epidermidis S2 isolate with low expressions of genes encoding pyruvate dehydrogenase (pdh), and phosphate acetyltransferase (pta) was found to be poorly electrogenic. The protective action of electrogenic S. epidermidis against UV-B-induced skin injuries was considerably suppressed when mouse skin was applied with LCC in combination with a poorly electrogenic S. epidermidis S2 isolate. Exploring new indication of LCC for promoting S. epidermidis against UV-B provided an example of repurposing INCI-registered compounds as skin prebiotics.

scholarly journals A Role for Histone H2B During Repair of UV-Induced DNA Damage in Saccharomyces cerevisiae

Genetics ◽  
2002 ◽  
Vol 160 (4) ◽  
pp. 1375-1387
Author(s):  
Emmanuelle M D Martini ◽  
Scott Keeney ◽  
Mary Ann Osley
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Chromatin Structure ◽  
Specific Effect ◽  
Cell Killing ◽  
Cyclobutane Pyrimidine Dimers ◽  
Histone H2b ◽  
Uv Sensitivity ◽  
Pyrimidine Dimers

Abstract To investigate the role of the nucleosome during repair of DNA damage in yeast, we screened for histone H2B mutants that were sensitive to UV irradiation. We have isolated a new mutant, htb1-3, that shows preferential sensitivity to UV-C. There is no detectable difference in bulk chromatin structure or in the number of UV-induced cis-syn cyclobutane pyrimidine dimers (CPD) between HTB1 and htb1-3 strains. These results suggest a specific effect of this histone H2B mutation in UV-induced DNA repair processes rather than a global effect on chromatin structure. We analyzed the UV sensitivity of double mutants that contained the htb1-3 mutation and mutations in genes from each of the three epistasis groups of RAD genes. The htb1-3 mutation enhanced UV-induced cell killing in rad1Δ and rad52Δ mutants but not in rad6Δ or rad18Δ mutants, which are defective in postreplicational DNA repair (PRR). When combined with other mutations that affect PRR, the histone mutation increased the UV sensitivity of strains with defects in either the error-prone (rev1Δ) or error-free (rad30Δ) branches of PRR, but did not enhance the UV sensitivity of a strain with a rad5Δ mutation. When combined with a ubc13Δ mutation, which is also epistatic with rad5Δ, the htb1-3 mutation enhanced UV-induced cell killing. These results suggest that histone H2B acts in a novel RAD5-dependent branch of PRR.

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