title: Effects of tet-induced oxidation products of 5-methylcytosine on DNA replication in mammalian cells.
abstract: 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.
authors: Department of Chemistry, University of California , Riverside, California 92521, United States.
authors: Debin
authors: D
authors: Ji
authors: Changjun
authors: C
authors: You
authors: Pengcheng
authors: P
authors: Wang
authors: Yinsheng
authors: Y
authors: Wang
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D049308:Dioxygenases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009838:Oligodeoxyribonucleotides; D010084:Oxidation-Reduction; D011518:Proto-Oncogene Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D044503:5-Methylcytosine; D049308:Dioxygenases