5-Formylcytosine does not change the global structure of DNA.

5-Formylcytosine does not change the global structure of DNA.
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DOI:
10.1038/nsmb.3411
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发表时间:
2017-06
影响因子:
16.8
通讯作者:
Brown T
Brown T
中科院分区:
生物学1区
文献类型:
--
作者:
Hardwick JS;Ptchelkine D;El-Sagheer AH;Tear I;Singleton D;Phillips SEV;Lane AN;Brown T

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5-甲酰胞嘧啶(fC)被参与表观遗传修饰和DNA阅读的酶识别的机制尚不清楚,最近提出了一种不寻常的DNA结构(F-DNA)作为fC簇的酶识别的基础。我们使用NMR和X射线晶体学比较了几种修饰的DNA双链体与未修饰的类似物,并表明在晶体状态下它们都属于A家族,但在溶液中它们都是B家族的成员。与以前的研究相反,我们发现,5-甲酰胞嘧啶并没有显着影响DNA的结构,虽然有适度的局部差异,在修饰位点。因此,全球构象的变化是不太可能占这个修改后的基地的承认,我们的结构数据有利于一种机制,在碱基对分辨率的识别5-甲酰胞嘧啶表观基因组修饰酶。
The mechanism by which 5-formylcytosine (fC) is recognised by enzymes involved in epigenetic modification and reading of DNA is not known, and recently an unusual DNA structure (F-DNA) was proposed as the basis for enzyme recognition of clusters of fC. We used NMR and X-ray crystallography to compare several modified DNA duplexes with the unmodified analogues and show that in the crystal state they all belong to the A-family, but in solution they are all members of the B-family. Contrary to the previous study, we find that 5-formylcytosine does not significantly affect the structure of DNA, though there are modest local differences at the modification sites. Hence, global conformation changes are unlikely to account for the recognition of this modified base, and our structural data favour a mechanism that operates at base-pair resolution for the recognition of 5-formylcytosine by epigenome-modifying enzymes.
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