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

AI Article Synopsis

  • - Methylation of cytosine (5meC) is an important epigenetic mark in eukaryotes that helps maintain gene regulation and is preserved during DNA replication by specific enzymes called DNMTs.
  • - Different animal lineages show a varied presence of DNA methylation, with some losing it entirely, while basal nematodes show retention of methylation concentrated on repeat sequences.
  • - The study suggests a co-evolution of DNA methylation mechanisms and the enzyme ALKB2, while also linking DNMT activity to the introduction of harmful DNA lesions, which could contribute to the reduction of DNA methylation in various species.

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865749PMC
http://dx.doi.org/10.1038/s41588-018-0061-8DOI Listing

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