Area A: Modifications on Nucleic Acids

Project A04 – Molecular mechanism of active demethylation

Since 2009 three new DNA bases (5-hydroxymethyl-, 5-formyl-, and 5-carboxy-cytidine, hmdC, fdC and cadC) were discovered that are present in the DNA isolated from stem cells and neurons. We believe that fdC and cadC undergo deformylation and decarboxylation reactions to establish a new, long search for, pathway to active demethylation. In this project, we plan to gain direct in vivo evidence for the existence of the putative decarboxylation reaction and we plan to make the first steps towards identifying the decarboxylating entity in stem cells. In the second part of the project, we plan to develop new, robust sequencing methods that will allow us to determine the positions of hmdC and fdC in the genome..