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Description
Processes such as transcription, repair and replication that require efficient DNA recognition are dependent on modulation of chromatin structure. Chromatin relaxation is a critical event that occurs during DNA repair and is associated with the negatively charged polymer of adenosine 5'-diphosphate (ADP)-ribose (PAR). PAR is synthesized from nicotinamide adenine dinucleotide (NAD+) by the poly(ADP-ribose) polymerase protein family (PARPs), of which PARP-1 (and to a lesser extent PARP-2) respond to DNA-strand breaks. PARP-1 is selectively activated by DNA strand breaks to catalyze the addition of long branched chains of PAR to a variety of nuclear proteins, most notably PARP itself. The amount of PAR formed in living cells with DNA damage is commensurate with the extent of the damage. Under DNA damage conditions, PAR undergoes a rapid turnover, with a half-life in the range of minutes, as PAR is rapidly hydrolyzed and converted to free ADP-ribose by the enzyme poly(ADP-ribose)glycohydrolase (PARG). PAR regulates not only cell survival and cell-death programmes, but also an increasing number of other biological functions with which novel members of the PARP family have been associated. These include transcriptional regulation, cell division, intracellular trafficking, inflammation and energy metabolism.