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. Author manuscript; available in PMC: 2014 Dec 1.
Published in final edited form as: Mol Aspects Med. 2013 Apr 25;34(6):10.1016/j.mam.2013.04.001. doi: 10.1016/j.mam.2013.04.001

Figure 2. Two pathways of PARP1 activation.

Figure 2

1. PARP1 is broadly distributed in chromatin as it interacts with core histones of nucleosomes. PARP1 is inactive in this state because of inhibitory effect of histone H2A. 2. Genotoxic stress –dependent PARP1 activation. N-terminal domain of PARP1 serves as a sensor of the double strand breaks and nicks in genomic DNA. Upon binding to damaged DNA, PARP1 mediates conformational changes in nucleosomes leading to disruption of interaction with histones and consequent activation of the PARP1 enzymatic reaction. 3. DNA-independent PARP1 activation. Developmental or environmental signals induce local changes in the “histone modification code” and subsequently expose N-tail of histone H4 and/or hide histone H2A. These structural changes are followed by H4-dependent PARP1 activation.