5-Formylcytosine does not change the global structure of DNA

Jack S. Hardwick; Denis Ptchelkine; Afaf H. El-Sagheer; Ian Tear; Daniel Singleton; Simon E.V. Phillips; Andrew N. Lane; Tom Brown

doi:10.1038/nsmb.3411

5-Formylcytosine does not change the global structure of DNA

Jack S. Hardwick, Denis Ptchelkine, Afaf H. El-Sagheer, Ian Tear, Daniel Singleton, Simon E.V. Phillips, Andrew N. Lane, Tom Brown

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

Abstract

The mechanism by which the recently identified DNA modification 5-formylcytosine (f C) is recognized by epigenetic writer and reader proteins is not known. Recently, an unusual DNA structure, F-DNA, has been proposed as the basis for enzyme recognition of clusters of f C. We used NMR and X-ray crystallography to compare several modified DNA duplexes with unmodified analogs and found that in the crystal state the duplexes all belong to the A family, whereas in solution they are all members of the B family. We found that, contrary to previous findings, f C does not significantly affect the structure of DNA, although 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 favor a mechanism that operates at base-pair resolution for the recognition of f C by epigenome-modifying enzymes.

Original language	English
Pages (from-to)	544-552
Number of pages	9
Journal	Nature Structural and Molecular Biology
Volume	24
Issue number	6
DOIs	https://doi.org/10.1038/nsmb.3411
State	Published - Jun 6 2017

Bibliographical note

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© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.

Funding

Funders	Funder number
National Childhood Cancer Registry – National Cancer Institute	P30CA177558

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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10.1038/nsmb.3411

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title = "5-Formylcytosine does not change the global structure of DNA",

abstract = "The mechanism by which the recently identified DNA modification 5-formylcytosine (f C) is recognized by epigenetic writer and reader proteins is not known. Recently, an unusual DNA structure, F-DNA, has been proposed as the basis for enzyme recognition of clusters of f C. We used NMR and X-ray crystallography to compare several modified DNA duplexes with unmodified analogs and found that in the crystal state the duplexes all belong to the A family, whereas in solution they are all members of the B family. We found that, contrary to previous findings, f C does not significantly affect the structure of DNA, although 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 favor a mechanism that operates at base-pair resolution for the recognition of f C by epigenome-modifying enzymes.",

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AU - Tear, Ian

AU - Singleton, Daniel

AU - Phillips, Simon E.V.

AU - Lane, Andrew N.

AU - Brown, Tom

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5-Formylcytosine does not change the global structure of DNA

Abstract

Bibliographical note

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