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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Autores principales: Xi-Wen Xing, Yu-Li Liu, Mario Vargas, Yinsheng Wang, Yu-Qi Feng, Xiang Zhou, Bi-Feng Yuan
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/66d7240d5cd04d0fbd511d3388ea3b33
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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 AT xiwenxing mutagenicandcytotoxicpropertiesofoxidationproductsof5methylcytosinerevealedbynextgenerationsequencing
AT yuliliu mutagenicandcytotoxicpropertiesofoxidationproductsof5methylcytosinerevealedbynextgenerationsequencing
AT mariovargas mutagenicandcytotoxicpropertiesofoxidationproductsof5methylcytosinerevealedbynextgenerationsequencing
AT yinshengwang mutagenicandcytotoxicpropertiesofoxidationproductsof5methylcytosinerevealedbynextgenerationsequencing
AT yuqifeng mutagenicandcytotoxicpropertiesofoxidationproductsof5methylcytosinerevealedbynextgenerationsequencing
AT xiangzhou mutagenicandcytotoxicpropertiesofoxidationproductsof5methylcytosinerevealedbynextgenerationsequencing
AT bifengyuan mutagenicandcytotoxicpropertiesofoxidationproductsof5methylcytosinerevealedbynextgenerationsequencing
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