DNA Bases beyond Watson and Crick
Epigenetic information is for example stored in the form of modified bases in the genome. The positions and the kind of the base modifications is one factor that determines the identity of the corresponding cell. Setting and erasing of epigenetic imprints is one factor that controls the development process from a zygote over an omnipotent stem cells to finally an adult specialized cell. The underlying biochemical mechanism are largely unknown. I am going to discuss results related to the function and distribution of the new epigenetic bases 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), 5-carboxycytosine (caC), and 5-hydroxymethyluracil. These nucleobases seem to control epigenetic programming of cells. Synthetic routes to these new bases and isotope derivatives will be discussed that enable the preparation of oligonucleotides and allow high end mass spectrometry studies to decipher the biological functions of the new bases. In particular, results from quantitative mass spectrometry, new covalent-capture proteomics mass spectrometry and isotope tracing techniques will be reported. Finally I am dicussing potential präbiotic origins of modified bases.
Center for Integrative Protein Science at the Department of Chemistry, Ludwig Maximilians University, Munich, Butenandtstr. 5-13, 81377; www.carellgroup.de
Domain 4 - UMR 3666 / U1143 - Chemical Biology of Membranes and Therapeutic Delivery