Extended Data Fig. 11: Depicting the function of NuMA in response to oxidative stress.
From: A mechanism for oxidative damage repair at gene regulatory elements
(a) Distribution of PARP1/NuMA expression across brain tissues of the GTEx v8 dataset. (b) A schematic diagram depicting NuMA’s role in response to oxidative stress. NuMA is enriched at the promoters and interacts with RNA Polymerase 2 (Pol2) and the SSBR proteins, TDP1 and PARP1. As a result of the enrichment of this complex, cells are efficient at repairing oxidative damage at promoters. NuMA acts as a PAR sink, ensuring the physiological levels of Pol2 PARylation that takes place in the nucleoplasm and thus increases the availability of Pol2 at promoters and enhances its release from pausing. This results in increasing the transcription of NuMA regulated genes (NRGs) (c) Decreased levels of NuMA increases the oxidative damage at promoters. Moreover, the absence of NuMA increases Pol2 PARylation in the nucleoplasm, thereby decreasing Pol2 availability at promoters, resulting in a reduction of the transcription of NRGs.
