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

MU Musheev, A Baumgärtner, L Krebs… - Nature chemical …, 2020 - nature.com
MU Musheev, A Baumgärtner, L Krebs, C Niehrs
Nature chemical biology, 2020nature.com
The proposal that N 6-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-N 6-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.
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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