A spontaneous ring-opening reaction leads to a repair‐resistant thymine oxidation product in genomic DNA
The alphabet of modified DNA bases goes beyond the conventional four letters, with biological roles being found for many such modifications. Herein, we describe the observation of a modified thymine base that arises from spontaneous N1−C2 ring opening of the oxidation product 5‐formyl uracil, after...
| Glavni autori: | , , , |
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| Format: | Journal article |
| Jezik: | English |
| Izdano: |
Wiley
2019
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| _version_ | 1826272768464781312 |
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| author | Sahakyan, A Mahtey, A Kawasaki, F Balasubramanian, S |
| author_facet | Sahakyan, A Mahtey, A Kawasaki, F Balasubramanian, S |
| author_sort | Sahakyan, A |
| collection | OXFORD |
| description | The alphabet of modified DNA bases goes beyond the conventional four letters, with biological roles being found for many such modifications. Herein, we describe the observation of a modified thymine base that arises from spontaneous N1−C2 ring opening of the oxidation product 5‐formyl uracil, after N3 deprotonation. We first observed this phenomenon in silico through ab initio calculations, followed by in vitro experiments to verify its formation at a mononucleoside level and in a synthetic DNA oligonucleotide context. We show that the new base modification (Trex, thymine ring expunged) can form under physiological conditions, and is resistant to the action of common repair machineries. Furthermore, we found cases of the natural existence of Trex while screening a number of human cell types and mESC (E14), thus suggesting potential biological relevance of this modification. |
| first_indexed | 2024-03-06T22:17:48Z |
| format | Journal article |
| id | oxford-uuid:5401d40f-4c21-4120-837d-8e2b7961ce2e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:17:48Z |
| publishDate | 2019 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:5401d40f-4c21-4120-837d-8e2b7961ce2e2022-03-26T16:35:05ZA spontaneous ring-opening reaction leads to a repair‐resistant thymine oxidation product in genomic DNAJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5401d40f-4c21-4120-837d-8e2b7961ce2eEnglishSymplectic Elements at OxfordWiley2019Sahakyan, AMahtey, AKawasaki, FBalasubramanian, SThe alphabet of modified DNA bases goes beyond the conventional four letters, with biological roles being found for many such modifications. Herein, we describe the observation of a modified thymine base that arises from spontaneous N1−C2 ring opening of the oxidation product 5‐formyl uracil, after N3 deprotonation. We first observed this phenomenon in silico through ab initio calculations, followed by in vitro experiments to verify its formation at a mononucleoside level and in a synthetic DNA oligonucleotide context. We show that the new base modification (Trex, thymine ring expunged) can form under physiological conditions, and is resistant to the action of common repair machineries. Furthermore, we found cases of the natural existence of Trex while screening a number of human cell types and mESC (E14), thus suggesting potential biological relevance of this modification. |
| spellingShingle | Sahakyan, A Mahtey, A Kawasaki, F Balasubramanian, S A spontaneous ring-opening reaction leads to a repair‐resistant thymine oxidation product in genomic DNA |
| title | A spontaneous ring-opening reaction leads to a repair‐resistant thymine oxidation product in genomic DNA |
| title_full | A spontaneous ring-opening reaction leads to a repair‐resistant thymine oxidation product in genomic DNA |
| title_fullStr | A spontaneous ring-opening reaction leads to a repair‐resistant thymine oxidation product in genomic DNA |
| title_full_unstemmed | A spontaneous ring-opening reaction leads to a repair‐resistant thymine oxidation product in genomic DNA |
| title_short | A spontaneous ring-opening reaction leads to a repair‐resistant thymine oxidation product in genomic DNA |
| title_sort | spontaneous ring opening reaction leads to a repair resistant thymine oxidation product in genomic dna |
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