Longevity & AgingScientists Map How DNA Damage Triggers a Double Chemical Tag on Histones
A team at the Max Planck Institute for Biology of Ageing has discovered that serine ADP-ribosylation (Ser-ADPr), a DNA-damage-induced chemical tag placed on histones and PARP1 by the enzyme PARP1/HPF1, is itself a substrate for a second modification: ester-linked ubiquitylation. Using custom proteomics tools and a novel enrichment strategy built around the RNF114 protein's dual-recognition domains, they pinpointed exact sites on histones and PARP1 where this rare composite modification occurs. They also engineered a detection reagent enabling routine laboratory identification of this dual mark. The findings establish ADP-ribosyl-ubiquitylation as a genuine endogenous post-translational modification and open new avenues for understanding DNA repair, chromatin regulation, and potentially aging-related cellular processes.
