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Effects of Tet-Induced Oxidation Products of 5-Methylcytosine on DNA Replication in Mammalian Cells

[Image: see text] Recently 5-hydroxymethyl-2′-deoxycytidine (5hmdC), 5-formyl-2′-deoxycytidine (5fdC), and 5-carboxyl-2′-deoxycytidine (5cadC) were discovered in mammalian DNA as oxidation products of 5-methyl-2′-deoxycytidine (5mdC) induced by the ten-eleven translocation family of enzymes. These o...

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Autores principales: Ji, Debin, You, Changjun, Wang, Pengcheng, Wang, Yinsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216192/
https://www.ncbi.nlm.nih.gov/pubmed/24979327
http://dx.doi.org/10.1021/tx500169u
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author Ji, Debin
You, Changjun
Wang, Pengcheng
Wang, Yinsheng
author_facet Ji, Debin
You, Changjun
Wang, Pengcheng
Wang, Yinsheng
author_sort Ji, Debin
collection PubMed
description [Image: see text] Recently 5-hydroxymethyl-2′-deoxycytidine (5hmdC), 5-formyl-2′-deoxycytidine (5fdC), and 5-carboxyl-2′-deoxycytidine (5cadC) were discovered in mammalian DNA as oxidation products of 5-methyl-2′-deoxycytidine (5mdC) induced by the ten-eleven translocation family of enzymes. These oxidized derivatives of 5mdC may not only act as intermediates of active cytosine demethylation in mammals but also serve as epigenetic marks on their own. It remains unclear how 5hmdC, 5fdC, and 5cadC affect DNA replication in mammalian cells. Here, we examined the effects of the three modified nucleosides on the efficiency and accuracy of DNA replication in HEK293T human kidney epithelial cells. Our results demonstrated that a single, site-specifically incorporated 5fdC or 5cadC conferred modest drops, by approximately 30%, in replication bypass efficiency without inducing detectable mutations in human cells, whereas replicative bypass of 5hmdC is both accurate and efficient. The lack of pronounced perturbation of these oxidized 5mdC derivatives on DNA replication is consistent with their roles in epigenetic regulation of gene expression.
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spelling pubmed-42161922015-06-30 Effects of Tet-Induced Oxidation Products of 5-Methylcytosine on DNA Replication in Mammalian Cells Ji, Debin You, Changjun Wang, Pengcheng Wang, Yinsheng Chem Res Toxicol [Image: see text] Recently 5-hydroxymethyl-2′-deoxycytidine (5hmdC), 5-formyl-2′-deoxycytidine (5fdC), and 5-carboxyl-2′-deoxycytidine (5cadC) were discovered in mammalian DNA as oxidation products of 5-methyl-2′-deoxycytidine (5mdC) induced by the ten-eleven translocation family of enzymes. These oxidized derivatives of 5mdC may not only act as intermediates of active cytosine demethylation in mammals but also serve as epigenetic marks on their own. It remains unclear how 5hmdC, 5fdC, and 5cadC affect DNA replication in mammalian cells. Here, we examined the effects of the three modified nucleosides on the efficiency and accuracy of DNA replication in HEK293T human kidney epithelial cells. Our results demonstrated that a single, site-specifically incorporated 5fdC or 5cadC conferred modest drops, by approximately 30%, in replication bypass efficiency without inducing detectable mutations in human cells, whereas replicative bypass of 5hmdC is both accurate and efficient. The lack of pronounced perturbation of these oxidized 5mdC derivatives on DNA replication is consistent with their roles in epigenetic regulation of gene expression. American Chemical Society 2014-06-30 2014-07-21 /pmc/articles/PMC4216192/ /pubmed/24979327 http://dx.doi.org/10.1021/tx500169u Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Ji, Debin
You, Changjun
Wang, Pengcheng
Wang, Yinsheng
Effects of Tet-Induced Oxidation Products of 5-Methylcytosine on DNA Replication in Mammalian Cells
title Effects of Tet-Induced Oxidation Products of 5-Methylcytosine on DNA Replication in Mammalian Cells
title_full Effects of Tet-Induced Oxidation Products of 5-Methylcytosine on DNA Replication in Mammalian Cells
title_fullStr Effects of Tet-Induced Oxidation Products of 5-Methylcytosine on DNA Replication in Mammalian Cells
title_full_unstemmed Effects of Tet-Induced Oxidation Products of 5-Methylcytosine on DNA Replication in Mammalian Cells
title_short Effects of Tet-Induced Oxidation Products of 5-Methylcytosine on DNA Replication in Mammalian Cells
title_sort effects of tet-induced oxidation products of 5-methylcytosine on dna replication in mammalian cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216192/
https://www.ncbi.nlm.nih.gov/pubmed/24979327
http://dx.doi.org/10.1021/tx500169u
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