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Biological Chemistry

Modified Base Loosens Up DNA

Conformation change caused by 5-formylcytosine may aid demethylation and transcription

by Stu Borman
December 22, 2014 | APPEARED IN VOLUME 92, ISSUE 51

Researchers have discovered how a modified DNA base may regulate cellular function. 5-Formylcytosine (5fC), a modified cytosine, is believed to help control demethylation and gene expression, but how it functions has been unknown. Shankar Balasubramanian and coworkers at the University of Cambridge now find that 5fC’s presence causes localized conformational changes in duplex DNA (Nat. Struct. Mol. Biol. 2014, DOI: 10.1038/nsmb.2936). Their X-ray structure of double-stranded DNA containing a 5fC cluster shows that it adopts a unique conformation, which they call F-DNA. This bulge is wound less tightly than normal DNA, which might ease intervention by a demethylation enzyme or transcription factors. But chemical biologist Chuan He of the University of Chicago comments that “the formation of clusters of 5fC and potential impacts on DNA conformation in vivo still need to be further studied and confirmed.”

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Credit: Nat. Struct. Mol. Biol.
DNA sequences with conventional bases adopt the classic double-helical conformation (top), whereas the modified base 5-formylcytosine causes the helix to bulge and loosen (bottom). This conformation, called F-DNA, may help control gene expression.
09251-scicon-unwinding1.jpg
Credit: Nat. Struct. Mol. Biol.
DNA sequences with conventional bases adopt the classic double-helical conformation (top), whereas the modified base 5-formylcytosine causes the helix to bulge and loosen (bottom). This conformation, called F-DNA, may help control gene expression.
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