N 6-Hydroxymethyladenine: a hydroxylation derivative of N6-methyladenine in genomic DNA of mammals.

Nucleic Acids Res

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan 430072, P.R. China.

Published: February 2019

AI Article Synopsis

  • m6dA is a newly-discovered form of DNA methylation that's being studied for its potential role as an epigenetic mark in eukaryotes, similar to m5dC.
  • Researchers found a new DNA modification called hm6dA, created from m6dA through a process involving the ALKBH1 protein in mammals.
  • The levels of hm6dA are significantly higher in lung carcinoma tissues, suggesting that the expression of ALKBH1 may be linked to this increase.

Article Abstract

In addition to DNA cytosine methylation (5-methyl-2'-deoxycytidine, m5dC), DNA adenine methylation (N6-methyl-2'-deoxyadenosine, m6dA) is another DNA modification that has been discovered in eukaryotes. Recent studies demonstrated that the content and distribution of m6dA in genomic DNA of vertebrates and mammals exhibit dynamic regulation, indicating m6dA may function as a potential epigenetic mark in DNA of eukaryotes besides m5dC. Whether m6dA undergoes the further oxidation in a similar way to m5dC remains elusive. Here, we reported the existence of a new DNA modification, N6-hydroxymethyl-2'-deoxyadenosine (hm6dA), in genomic DNA of mammalian cells and tissues. We found that hm6dA can be formed from the hydroxylation of m6dA by the Fe2+- and 2-oxoglutarate-dependent ALKBH1 protein in genomic DNA of mammals. In addition, the content of hm6dA exhibited significant increase in lung carcinoma tissues. The increased expression of ALKBH1 in lung carcinoma tissues may contribute to the increase of hm6dA in DNA. Taken together, our study reported the existence and formation of hm6dA in genomic DNA of mammals.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379677PMC
http://dx.doi.org/10.1093/nar/gky1218DOI Listing

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