“Chromatin ADP-ribosylation in neurodegenerative disease”

ADP-ribosylation is a common protein post-translational modification that regulates numerous cellular processes, including transcription, cell proliferation and differentiation, immune and stress responses, aging, and cell death. One of its most extensively studied roles is in DNA damage response and subsequent DNA repair. Moreover, deregulation of ADP-ribose metabolism is linked to neurological and neurodevelopmental disorders. Interestingly, our recent work reveals that serine ADP-ribosylation is largely dispensable for DNA repair. We propose that deregulated serine ADP-ribosylation might instead lead to alterations in other histone modifications, changes in chromatin remodeling and gene expression, and consequently could contribute to the development of neurological diseases.