No evidence for DNA N6-methyladenine in mammals

No evidence for DNA N6-methyladenine in mammals
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DOI:
10.1126/sciadv.aay3335
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发表时间:
2020-03-01
期刊:
影响因子:
13.6
通讯作者:
Nestor, Coim E.
Nestor, Coim E.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Douvlataniotis, Karolos;Bensberg, Maike;Nestor, Coim E.

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N-6-甲基腺嘌呤(6mdA)是细菌中广泛存在的一种DNA修饰。最近,在哺乳动物的DNA中也发现了6mdA。然而,不同研究之间对6mdA丰度和分布的测量往往非常不同,即使是在来自相同哺乳动物细胞类型的DNA上也是如此。利用对已发表数据的全面生物信息学分析和新的实验方法,我们揭示了在哺乳动物中检测6mdA的努力已经受到细菌污染、RNA污染、技术限制和抗体非特异性的严重影响。这些并发症使6mdA成为研究的一个特别有问题的DNA修饰,并导致在几个哺乳动物系统中错误检测6mdA。总而言之,我们的结果强烈表明,到目前为止发表的证据不足以支持哺乳动物中存在6mdA。
N-6-methyladenine (6mdA) is a widespread DNA modification in bacteria. More recently, 6mdA has also been characterized in mammalian DNA. However, measurements of 6mdA abundance and profiles are often very dissimilar between studies, even when performed on DNA from identical mammalian cell types. Using comprehensive bioinformatics analyses of published data and novel experimental approaches, we reveal that efforts to assay 6mdA in mammals have been severely compromised by bacterial contamination, RNA contamination, technological limitations, and antibody nonspecificity. These complications render 6mdA an exceptionally problematic DNA modification to study and have resulted in erroneous detection of 6mdA in several mammalian systems. Together, our results strongly imply that the evidence published to date is not sufficient to support the presence of 6mdA in mammals.