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

The origin of genomic N6-methyl-deoxyadenosine in mammalian cells
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DOI:
10.1038/s41589-020-0504-2
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发表时间:
2020-03-23
影响因子:
14.8
通讯作者:
Niehrs, Christof
Niehrs, Christof
中科院分区:
生物学1区
文献类型:
--
作者:
Musheev, Michael U.;Baumgaertner, Anne;Niehrs, Christof

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关于N-6-甲基脱氧腺苷(m(6)da)作为哺乳动物表观遗传标记的提议仍然存在争议。利用同位素标记结合超灵敏质谱仪,我们证实了哺乳动物DNA中存在低水平的m(6)da。然而,基因组m(6)da的大部分来自于核糖核酸-N-6-甲基腺苷,它是通过核苷酸回收途径加工的,并被DNA聚合酶错误结合。我们的结果反对m(6)da在哺乳动物细胞中作为可遗传的表观遗传DNA标记。
The proposal that N-6-methyl-deoxyadenosine (m(6)dA) acts as an epigenetic mark in mammals remains controversial. Using isotopic labeling coupled to ultrasensitive mass spectrometry, we confirm the presence of low-level m(6)dA in mammalian DNA. However, the bulk of genomic m(6)dA originates from ribo-N-6-methyladenosine, which is processed via the nucleotide-salvage pathway and misincorporated by DNA polymerases. Our results argue against m(6)dA acting as a heritable, epigenetic DNA mark in mammalian cells.