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In the human body, nearly all cells share the same genetic material, yet they perform distinct functions due to the activation of different genes. This differentiation requires precise control of gene expression, involving both stable and dynamic activation and silencing of genes. The DNA base sequence alone cannot manage these processes; cytosine bases can be further modified to regulate gene activity. Methylated cytosines are known to silence genes, and abnormal methylation is linked to diseases, including cancer. Detecting methylated cytosines has been enhanced by a methodology that distinguishes between cytosine and methylcytosine using O-Allylhydroxylamine, with different reaction products identifiable through pyrosequencing. Additionally, methylcytosine can oxidize to hydroxymethylcytosine, which was found in high amounts in the central nervous system, increasing during brain development and decreasing in cancerous tissues. Further oxidation to formylcytosine and carboxylcytosine was explored as a potential mechanism for active DNA demethylation. This research led to the identification of these constituents in mammalian DNA. The study also synthesized natural and isotope-labeled nucleosides for new phosphoramidite building blocks. Furthermore, the impact of UV light on CpG dinucleotides was examined, revealing new UV-induced DNA photolesions that disrupt both genomic integrity and epigenetic information.
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Synthesis of natural dna modifications and their detection in DNA, Martin Munzel
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- Année de publication
- 2011
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