TY - JOUR
T1 - 5-Formylcytosine does not change the global structure of DNA
AU - Hardwick, Jack S.
AU - Ptchelkine, Denis
AU - El-Sagheer, Afaf H.
AU - Tear, Ian
AU - Singleton, Daniel
AU - Phillips, Simon E.V.
AU - Lane, Andrew N.
AU - Brown, Tom
N1 - Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2017/6/6
Y1 - 2017/6/6
N2 - 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.
AB - 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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U2 - 10.1038/nsmb.3411
DO - 10.1038/nsmb.3411
M3 - Article
C2 - 28504696
AN - SCOPUS:85020460816
SN - 1545-9993
VL - 24
SP - 544
EP - 552
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 6
ER -