1. Academic Validation
  2. The origin of genomic N6-methyl-deoxyadenosine in mammalian cells

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

Affiliations

  • 1 Institute of Molecular Biology gGmbH, Mainz, Germany. M.Musheev@IMB-mainz.de.
  • 2 Institute of Molecular Biology gGmbH, Mainz, Germany.
  • 3 Institute of Molecular Biology gGmbH, Mainz, Germany. C.Niehrs@IMB-mainz.de.
  • 4 Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany. C.Niehrs@IMB-mainz.de.
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.

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