Genome dynamics in cell programming, aging and human disease
DNA in our cells is continuously damaged through its exposure to reactive agents of endogenous or environmental origin. Damage to DNA, however, does not only occur randomly by chemical reactions, but also on purpose, by the action of enzymes, to increase genetic variance or alter cell fate determining epigenetic marks, i.e., DNA methylation. Modifications of either kind occur thousands of times in our DNA every day and need to be controlled if genome integrity is to be maintained. We investigate molecular mechanisms underlying this dynamic instability of genomes. Over the past years, our research focus has been the role of DNA repair in DNA demethylation and its contribution to the patterning and maintenance of epigenetic programs – hence – cell identity. We have been following three main lines of investigation towards (i) unraveling the basic molecular mechanisms and function of active DNA demethylation, (ii) the relevance of DNA methylation control and stability for human aging and disease, and (iii) the impact of the environment on the stability of DNA methylation.