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 journalArticle

202 Citations (Scopus)

Abstract

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
Volume6
Early online date21 Sep 2014
DOIs
Publication statusPublished - 1 Dec 2014

Fingerprint

DNA
Labeling
Cells
5-Methylcytosine
Oxidation
Methylation
5-hydroxymethylcytosine
Cytosine
Liquid chromatography
Cell proliferation
Isotopes
Mass spectrometry
Health
Tissue
Derivatives

Cite this

Bachman, M., Uribe-Lewis, S., Yang, X., Williams, M., Murrell, A., & Balasubramanian, S. (2014). 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nature Chemistry, 6, 1049-1055. https://doi.org/10.1038/nchem.2064

5-Hydroxymethylcytosine is a predominantly stable DNA modification. / Bachman, Martin; Uribe-Lewis, Santiago; Yang, Xiaoping; Williams, Michael; Murrell, Adele; Balasubramanian, Shankar.

In: Nature Chemistry, Vol. 6, 01.12.2014, p. 1049-1055.

Research output: Contribution to journalArticle

Bachman, M, Uribe-Lewis, S, Yang, X, Williams, M, Murrell, A & Balasubramanian, S 2014, '5-Hydroxymethylcytosine is a predominantly stable DNA modification', Nature Chemistry, vol. 6, pp. 1049-1055. https://doi.org/10.1038/nchem.2064
Bachman M, Uribe-Lewis S, Yang X, Williams M, Murrell A, Balasubramanian S. 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nature Chemistry. 2014 Dec 1;6:1049-1055. https://doi.org/10.1038/nchem.2064
Bachman, Martin ; Uribe-Lewis, Santiago ; Yang, Xiaoping ; Williams, Michael ; Murrell, Adele ; Balasubramanian, Shankar. / 5-Hydroxymethylcytosine is a predominantly stable DNA modification. In: Nature Chemistry. 2014 ; Vol. 6. pp. 1049-1055.
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