5-Formylcytosine and 5-Carboxylcytosine Significantly Reduce the Catalytic Activity of Hhal DNA Methyltransferase

DNA methylation is an essential epigenetic modification, and found to be dynamically changed due to the ob- servation of active DNA demethylation. During active demethylation, 5-methylcytosine （5mC） was oxidized step- wise by ten-eleven translocation （TET） enzymes into 5-hydroxymethylcytosine （5hmc）...

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Published inChinese journal of chemistry Vol. 35; no. 6; pp. 853 - 856
Main Authors Hong, Tingting, Wu, Fan, Fu, Boshi, Yuan, Yushu, Xu, Jinglei, Wang, Tianlu, Zhou, Xiang
Format Journal Article
LanguageEnglish
Published Weinheim WILEY-VCH Verlag GmbH & Co. KGaA 01.06.2017
Wiley Subscription Services, Inc
Subjects
5-甲基胞嘧啶
5‐carboxylcytosine
5‐formylcytosine
Base excision repair
base flipping
Catalysis
Catalytic activity
Cytosine
Demethylation
Deoxyribonucleic acid
DNA
DNA methylation
DNA methyltransferase
DNA序列
DNA甲基化
DNA甲基转移酶
Enzymes
HhaI methyltransferase
Intermediates
Nucleotide sequence
Repair
Translocation
催化活性
去甲基化
碱基切除修复
羧基
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Summary:DNA methylation is an essential epigenetic modification, and found to be dynamically changed due to the ob- servation of active DNA demethylation. During active demethylation, 5-methylcytosine （5mC） was oxidized step- wise by ten-eleven translocation （TET） enzymes into 5-hydroxymethylcytosine （5hmc）, 5-formylcytosine （5fC）, and 5-carboxylcytosine （5caC）. Then, the subsequent excision of 5fC and 5caC combined with base excision repair further restored cytosine, which completes the demethylation process. Here, we report that 5-formylcytosine and 5-carboxylcytosine significantly reduce the activity of HhaI DNA methyltransferase to methylate target cytosines when present on the hemi-modified sequence of the complementary DNA. This finding demonstrates that 5fC and 5caC function as more than intermediates for active DNA demethylation.
Bibliography:31-1547/O6
DNA methylation is an essential epigenetic modification, and found to be dynamically changed due to the ob- servation of active DNA demethylation. During active demethylation, 5-methylcytosine （5mC） was oxidized step- wise by ten-eleven translocation （TET） enzymes into 5-hydroxymethylcytosine （5hmc）, 5-formylcytosine （5fC）, and 5-carboxylcytosine （5caC）. Then, the subsequent excision of 5fC and 5caC combined with base excision repair further restored cytosine, which completes the demethylation process. Here, we report that 5-formylcytosine and 5-carboxylcytosine significantly reduce the activity of HhaI DNA methyltransferase to methylate target cytosines when present on the hemi-modified sequence of the complementary DNA. This finding demonstrates that 5fC and 5caC function as more than intermediates for active DNA demethylation.
5-formylcytosine, 5-carboxylcytosine, Hhal methyltransferase, base flipping
ISSN:1001-604X
1614-7065
DOI:10.1002/cjoc.201600879