Fig. 6: Model for the contribution of H2A.X nucleosomes towards PARP1-mediated DNA repair.
From: PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome

A DNA damage hotspot is demarcated by H2A.X deposition. Subsequent to a double helix breakage event, PARP1 rapidly associates with the H2A.X-nucleosomal DSBs at high affinity. This ensures prompt activation of PARP1, initiating PARylation, and H2A.X is subsequently phosphorylated to γH2A.X, which further stabilizes the assembly. Even as the NAD+ concentration drops to low levels, the influence of γH2A.X supports continued PARylation.