Mutagenic and cytotoxic properties of oxidation products of 5-methylcytosine revealed by next-generation sequencing.
5-methylcytosine (5-mC) can be sequentially oxidized to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and finally to 5-carboxylcytosine (5-caC), which is thought to function in active DNA cytosine demethylation in mammals. Although the roles of 5-mC in epigenetic regulation of gene expr...
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2013
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oai:doaj.org-article:66d7240d5cd04d0fbd511d3388ea3b332021-11-18T08:55:15ZMutagenic and cytotoxic properties of oxidation products of 5-methylcytosine revealed by next-generation sequencing.1932-620310.1371/journal.pone.0072993https://doaj.org/article/66d7240d5cd04d0fbd511d3388ea3b332013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24066027/?tool=EBIhttps://doaj.org/toc/1932-62035-methylcytosine (5-mC) can be sequentially oxidized to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and finally to 5-carboxylcytosine (5-caC), which is thought to function in active DNA cytosine demethylation in mammals. Although the roles of 5-mC in epigenetic regulation of gene expression are well established, the effects of 5-hmC, 5-foC and 5-caC on DNA replication remain unclear. Here we report a systematic study on how these cytosine derivatives (5-hmC, 5-foC and 5-caC) perturb the efficiency and accuracy of DNA replication using shuttle vector technology in conjugation with next-g sequencing. Our results demonstrated that, in Escherichia coli cells, all the cytosine derivatives could induce CT transition mutation at frequencies of 0.17%-1.12%, though no effect on replication efficiency was observed. These findings provide an important new insight on the potential mutagenic properties of cytosine derivatives occurring as the intermediates of DNA demethylation.Xi-Wen XingYu-Li LiuMario VargasYinsheng WangYu-Qi FengXiang ZhouBi-Feng YuanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e72993 (2013) |
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Medicine R Science Q Xi-Wen Xing Yu-Li Liu Mario Vargas Yinsheng Wang Yu-Qi Feng Xiang Zhou Bi-Feng Yuan Mutagenic and cytotoxic properties of oxidation products of 5-methylcytosine revealed by next-generation sequencing. |
description |
5-methylcytosine (5-mC) can be sequentially oxidized to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and finally to 5-carboxylcytosine (5-caC), which is thought to function in active DNA cytosine demethylation in mammals. Although the roles of 5-mC in epigenetic regulation of gene expression are well established, the effects of 5-hmC, 5-foC and 5-caC on DNA replication remain unclear. Here we report a systematic study on how these cytosine derivatives (5-hmC, 5-foC and 5-caC) perturb the efficiency and accuracy of DNA replication using shuttle vector technology in conjugation with next-g sequencing. Our results demonstrated that, in Escherichia coli cells, all the cytosine derivatives could induce CT transition mutation at frequencies of 0.17%-1.12%, though no effect on replication efficiency was observed. These findings provide an important new insight on the potential mutagenic properties of cytosine derivatives occurring as the intermediates of DNA demethylation. |
format |
article |
author |
Xi-Wen Xing Yu-Li Liu Mario Vargas Yinsheng Wang Yu-Qi Feng Xiang Zhou Bi-Feng Yuan |
author_facet |
Xi-Wen Xing Yu-Li Liu Mario Vargas Yinsheng Wang Yu-Qi Feng Xiang Zhou Bi-Feng Yuan |
author_sort |
Xi-Wen Xing |
title |
Mutagenic and cytotoxic properties of oxidation products of 5-methylcytosine revealed by next-generation sequencing. |
title_short |
Mutagenic and cytotoxic properties of oxidation products of 5-methylcytosine revealed by next-generation sequencing. |
title_full |
Mutagenic and cytotoxic properties of oxidation products of 5-methylcytosine revealed by next-generation sequencing. |
title_fullStr |
Mutagenic and cytotoxic properties of oxidation products of 5-methylcytosine revealed by next-generation sequencing. |
title_full_unstemmed |
Mutagenic and cytotoxic properties of oxidation products of 5-methylcytosine revealed by next-generation sequencing. |
title_sort |
mutagenic and cytotoxic properties of oxidation products of 5-methylcytosine revealed by next-generation sequencing. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/66d7240d5cd04d0fbd511d3388ea3b33 |
work_keys_str_mv |
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