PARP1

PARP1 (poly(ADP-ribose) polymerase 1) is a nuclear enzyme and central sensor of DNA damage, especially single-strand breaks. When activated, it cleaves NAD+ and transfers ADP-ribose units onto itself and onto target proteins to build branched poly(ADP-ribose) (PAR) chains. PAR signals recruit base excision repair factors, modulate chromatin structure and coordinate the early DNA damage response. Because PARP1 consumes substantial amounts of NAD+, chronic or excessive activation in ageing tissues with accumulating DNA damage can deplete cellular NAD+ pools, reducing the activity of NAD+-dependent enzymes such as sirtuins and impairing mitochondrial function. The NAD+-PARP1-sirtuin axis is therefore a central node connecting genome maintenance, energy metabolism and ageing, and is a target of NAD+ precursor and PARP inhibitor strategies.