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The Methylation Game: Epigenetic and Epitranscriptomic Dynamics of 5-Methylcytosine

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FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.915685

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DNA; RNA; m(5)C; hm(5)C; methyltransferases; demethylases; cancer; DNA damage

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The dynamics of DNA and RNA methylation are closely related to cellular processes such as development, differentiation, and genome integrity. Dysregulation of methyltransferases and demethylase enzymes has been associated with genome instability and cancer progression. Additionally, post-transcriptional DNA/RNA modifications play important roles in cellular function and the response to environmental cues. m(5)C, a key modification, has been identified as a regulator of the DNA damage response, although its mechanisms of deposition and removal and its role within the cell are still not fully understood.
DNA and RNA methylation dynamics have been linked to a variety of cellular processes such as development, differentiation, and the maintenance of genome integrity. The correct deposition and removal of methylated cytosine and its oxidized analogues is pivotal for cellular homeostasis, rapid responses to exogenous stimuli, and regulated gene expression. Uncoordinated expression of DNA/RNA methyltransferases and demethylase enzymes has been linked to genome instability and consequently to cancer progression. Furthermore, accumulating evidence indicates that post-transcriptional DNA/RNA modifications are important features in DNA/RNA function, regulating the timely recruitment of modification-specific reader proteins. Understanding the biological processes that lead to tumorigenesis or somatic reprogramming has attracted a lot of attention from the scientific community. This work has revealed extensive crosstalk between epigenetic and epitranscriptomic pathways, adding a new layer of complexity to our understanding of cellular programming and responses to environmental cues. One of the key modifications, m(5)C, has been identified as a contributor to regulation of the DNA damage response (DDR). However, the various mechanisms of dynamic m(5)C deposition and removal, and the role m(5)C plays within the cell, remains to be fully understood.

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