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MacroH2A1.1 is an endogenous inhibitor of PARP1. NMNAT1 acts as feeder providing NAD+ to PARP1. Activation of PARP1 is accompanied by auto-modification. Binding of the “tamer” macroH2A1.1 leads to its inhibition. The taming can be overcome by PARP1 hyperactivation and hypermodification. Proteins containing poly-ADP-ribose (PAR) interaction domains including macrodomains can act as readers of the ADP-ribose units. PARG and ARH3 are the erasers that remove PAR chains.
