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Evolutionary analysis indicates that DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity

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Title: Evolutionary analysis indicates that DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity
Authors: Rosic, S
Amouroux, R
Requena, C
Gomes, A
Rane, J
Beltran, T
Linnett, S
Emperle, M
Jeltsch, A
Selkirk, M
Grencis, R
Bancroft, A
Hajkova, P
Sarkies, P
Item Type: Journal Article
Abstract: Methylation at the 5 position of cytosine in DNA (5meC) is a key epigenetic mark in eukaryotes. Once introduced, 5meC can be maintained through DNA replication by the activity of ‘maintenance’ DNA methyltransferases (DNMTs). Despite their ancient origin, DNA methylation pathways differ widely across animals, such that 5meC is either confined to transcribed genes or lost altogether in several lineages. We used comparative epigenomics to investigate the evolution of DNA methylation. Although the model nematode Caenorhabditis elegans lacks DNA methylation, more basal nematodes retain cytosine DNA methylation, which is targeted to repeat loci. We found that DNA methylation coevolved with the DNA alkylation repair enzyme ALKB2 across eukaryotes. In addition, we found that DNMTs introduced the toxic lesion 3-methylcytosine into DNA both in vitro and in vivo. Alkylation damage is therefore intrinsically associated with DNMT activity, and this may promote the loss of DNA methylation in many species.
Issue Date: 19-Feb-2018
Date of Acceptance: 16-Jan-2018
URI: http://hdl.handle.net/10044/1/57228
DOI: https://dx.doi.org/10.1038/s41588-018-0061-8
ISSN: 1061-4036
Publisher: Nature Publishing Group
Start Page: 452
End Page: 459
Journal / Book Title: Nature Genetics
Volume: 50
Copyright Statement: © 2018 Nature America Inc., part of Springer Nature. All rights reserved.
Sponsor/Funder: Commission of the European Communities
EMBO
Commission of the European Communities
Medical Research Council
Funder's Grant Number: 257082
EMBO YIP
648879
MC-A652-5PZ80-3203-0000-0000
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
METHYLATION PATTERNS
DNMT3A
MUTATION
ANIMALS
GENOMES
PLANTS
CELLS
BASE
11 Medical And Health Sciences
06 Biological Sciences
Developmental Biology
Publication Status: Published
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine
Faculty of Natural Sciences



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