The origin of genomic N6-methyl-deoxyadenosine in mammalian cells

  • Nat Chem Biol. 2020 Jun;16(6):630-634. doi: 10.1038/s41589-020-0504-2.
Michael U Musheev  1 ,  Anne Baumgärtner  2 ,  Laura Krebs  2 ,  Christof Niehrs  3  4
Affiliations
  • 1. Institute of Molecular Biology gGmbH, Mainz, Germany. [email protected].
  • 2. Institute of Molecular Biology gGmbH, Mainz, Germany.
  • 3. Institute of Molecular Biology gGmbH, Mainz, Germany. [email protected].
  • 4. Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany. [email protected].
PMID: 32203414 DOI: 10.1038/s41589-020-0504-2
Abstract

The proposal that N6-methyl-deoxyadenosine (m6dA) acts as an epigenetic MARK in mammals remains controversial. Using isotopic labeling coupled to ultrasensitive mass spectrometry, we confirm the presence of low-level m6dA in mammalian DNA. However, the bulk of genomic m6dA originates from ribo-N6-methyladenosine, which is processed via the nucleotide-salvage pathway and misincorporated by DNA polymerases. Our results argue against m6dA acting as a heritable, epigenetic DNA MARK in mammalian cells.