5-Hydroxymethylcytosine is a predominantly stable DNA modification

Martin Bachman, Santiago Uribe-Lewis, Xiaoping Yang, Michael Williams, Adele Murrell, Shankar Balasubramanian

Research output: Contribution to journalArticlepeer-review

379 Citations (SciVal)


5-Hydroxymethylcytosine (hmC) is an oxidation product of 5-methylcytosine which is present in the deoxyribonucleic acid (DNA) of most mammalian cells. Reduction of hmC levels in DNA is a hallmark of cancers. Elucidating the dynamics of this oxidation reaction and the lifetime of hmC in DNA is fundamental to understanding hmC function. Using stable isotope labelling of cytosine derivatives in the DNA of mammalian cells and ultrasensitive tandem liquid-chromatography mass spectrometry, we show that the majority of hmC is a stable modification, as opposed to a transient intermediate. In contrast with DNA methylation, which occurs immediately during replication, hmC forms slowly during the first 30 hours following DNA synthesis. Isotopic labelling of DNA in mouse tissues confirmed the stability of hmC in vivo and demonstrated a relationship between global levels of hmC and cell proliferation. These insights have important implications for understanding the states of chemically modified DNA bases in health and disease.

Original languageEnglish
Pages (from-to)1049-1055
Number of pages7
JournalNature Chemistry
Issue number12
Early online date21 Sept 2014
Publication statusPublished - 1 Dec 2014


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