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. Author manuscript; available in PMC: 2014 Feb 1.
Published in final edited form as: Curr Opin Struct Biol. 2013 Jan 16;23(1):134–143. doi: 10.1016/j.sbi.2013.01.003

Figure 4. Model for DNA damage-dependent activation of PARP-1.

Figure 4

In the absence of DNA damage, PARP-1 domains exist in an extended, “beads-on-a-string” conformation. The HD serves as a modulator of PARP-1 activity, holding the ART in a rigid conformation. Upon detecting DNA damage the Zn1, Zn3, and WGR domains collapse together, forming a network of interdomain contacts that perturb the structure of the HD, displacing a “leucine switch” that decreases the stability of the catalytic domain and increases the catalytic activity. A more flexible, dynamic ART conformation is more efficient to perform the multi-step synthesis of poly(ADP-ribose). The collapsed conformation positions the automodication region adjacent to the catalytic domain, providing substrate specificity and contributing to an enhanced rate of poly(ADP-ribose) production.