Abstract
Epigenetic DNA modifications play a fundamental role in modulating gene expression and regulating cellular and developmental biological processes, thereby forming a second layer of information in DNA. The epigenetic 2′-deoxycytidine modification 5-methyl-2′-deoxycytidine, together with its enzymatic oxidation products (5-hydroxymethyl-2′-deoxycytidine, 5-formyl-2′-deoxycytidine, and 5-carboxyl-2′-deoxycytidine), are closely related to deactivation and reactivation of DNA transcription. Here, we combine sub-30-fs transient absorption spectroscopy with high-level correlated multiconfigurational CASPT2/MM computational methods, explicitly including the solvent, to obtain a unified picture of the photophysics of deoxycytidine-derived epigenetic DNA nucleosides. We assign all the observed time constants and identify the excited state relaxation pathways, including the competition of intersystem crossing and internal conversion for 5-formyl-2′-deoxycytidine and ballistic decay to the ground state for 5-carboxy-2′-deoxycytidine. Our work contributes to shed light on the role of epigenetic derivatives in DNA photodamage as well as on their possible therapeutic use.
Highlights
Epigenetic DNA modifications play a fundamental role in modulating gene expression and regulating cellular and developmental biological processes, thereby forming a second layer of information in DNA
E pigenetics, which is the study of heritable phenotype modifications that do not involve alterations in the genotype, is becoming a more and more important field of research, aiming to explain how living organisms adapt to external stimuli.[1]
Methylation of 2′-deoxycytidine at the C5 position of the nucleobase can lead to transcriptional silencing of the corresponding gene in certain genomic regions.2 5-Methyl-2′-deoxycytidine is a prevailing epigenetic modification that plays important roles in modulating gene expression and developmental processes, and its dysregulation may cause severe diseases, including cancer.[1,3−6] Demethylation of mdC back to dC reactivates the transcription of these genes; the process behind this demethylation remains not yet fully understood
Summary
Epigenetic DNA modifications play a fundamental role in modulating gene expression and regulating cellular and developmental biological processes, thereby forming a second layer of information in DNA.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
