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

Autor: Rošić S; MRC London Institute of Medical Sciences, London, UK.; Institute of Clinical Sciences, Imperial College London, London, UK., Amouroux R; MRC London Institute of Medical Sciences, London, UK.; Institute of Clinical Sciences, Imperial College London, London, UK., Requena CE; MRC London Institute of Medical Sciences, London, UK.; Institute of Clinical Sciences, Imperial College London, London, UK., Gomes A; MRC London Institute of Medical Sciences, London, UK.; Institute of Clinical Sciences, Imperial College London, London, UK., Emperle M; Institute of Biochemistry, Universität Stuttgart, Stuttgart, Germany., Beltran T; MRC London Institute of Medical Sciences, London, UK.; Institute of Clinical Sciences, Imperial College London, London, UK., Rane JK; MRC London Institute of Medical Sciences, London, UK.; Institute of Clinical Sciences, Imperial College London, London, UK., Linnett S; MRC London Institute of Medical Sciences, London, UK.; Institute of Clinical Sciences, Imperial College London, London, UK., Selkirk ME; Department of Life Sciences, Imperial College London, London, UK., Schiffer PH; Department of Ecology and Evolution, University College London, London, UK., Bancroft AJ; School of Biological Sciences and Wellcome Trust Centre for Cell Matrix Research, FBMH, MAHSC, University of Manchester, Manchester, UK., Grencis RK; School of Biological Sciences and Wellcome Trust Centre for Cell Matrix Research, FBMH, MAHSC, University of Manchester, Manchester, UK., Jeltsch A; Institute of Biochemistry, Universität Stuttgart, Stuttgart, Germany., Hajkova P; MRC London Institute of Medical Sciences, London, UK. petra.hajkova@lms.mrc.ac.uk.; Institute of Clinical Sciences, Imperial College London, London, UK. petra.hajkova@lms.mrc.ac.uk., Sarkies P; MRC London Institute of Medical Sciences, London, UK. psarkies@imperial.ac.uk.; Institute of Clinical Sciences, Imperial College London, London, UK. psarkies@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2018 Mar; Vol. 50 (3), pp. 452-459. Date of Electronic Publication: 2018 Feb 19.
DOI: 10.1038/s41588-018-0061-8
Abstrakt: 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.
Databáze: MEDLINE
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