Imperial College London
Alternate

ProfessorPetraHajkova

Faculty of Medicine, Institute of Clinical Sciences

Professor of Developmental Epigenetics
 
 
 
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Contact

 

+44 (0)20 7594 6754petra.hajkova Website

 
 
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Location

 

5.11CLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Dukatz:2019:10.1016/j.jmb.2019.06.015,
author = {Dukatz, M and Requena, CE and Emperle, M and Hajkova, P and Sarkies, P and Jeltsch, A},
doi = {10.1016/j.jmb.2019.06.015},
journal = {Journal of Molecular Biology},
pages = {3139--3145},
title = {Mechanistic insights into Cytosine-N3 Methylation by DNA Methyltransferase DNMT3A},
url = {http://dx.doi.org/10.1016/j.jmb.2019.06.015},
volume = {431},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Recently, it has been discovered that different DNA-(cytosine C5)-methyltransferases including DNMT3A generate low levels of 3mC [Rosic et al. (2018), Nat. Genet., 50, 452-459]. This reaction resulted in the co-evolution of DNMTs and ALKB2 DNA repair enzymes, but its mechanism remained elusive. Here, we investigated the catalytic mechanism of DNMT3A for cytosine N3 methylation. We generated several DNMT3A variants with mutated catalytic residues and measured their activities in 5mC and 3mC generation by liquid chromatography linked to tandem mass spectrometry. Our data suggest that the methylation of N3 instead of C5 is caused by an inverted binding of the flipped cytosine target base into the active-site pocket of the DNA methyltransferase, which is partially compatible with the arrangement of catalytic amino acid residues. Given that all DNA-(cytosine C5)-methyltransferases have a common catalytic mechanism, it is likely that other enzymes of this class generate 3mC following the same mechanism.
AU  - Dukatz,M
AU  - Requena,CE
AU  - Emperle,M
AU  - Hajkova,P
AU  - Sarkies,P
AU  - Jeltsch,A
DO  - 10.1016/j.jmb.2019.06.015
EP  - 3145
PY  - 2019///
SN  - 0022-2836
SP  - 3139
TI  - Mechanistic insights into Cytosine-N3 Methylation by DNA Methyltransferase DNMT3A
T2  - Journal of Molecular Biology
UR  - http://dx.doi.org/10.1016/j.jmb.2019.06.015
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31229457
UR  - http://hdl.handle.net/10044/1/71573
VL  - 431
ER  -
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