[Report] ADP-ribose–derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling
Key nuclear processes in eukaryotes, including DNA replication, repair, and gene regulation, require extensive chromatin remodeling catalyzed by energy-consuming enzymes. It remains unclear how the ATP demands of such processes are met in response to rapid stimuli. We analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly(ADP-ribose) to ADP-ribose. In the presence of pyrophosphate, ADP-ribose is used by the pyrophosphatase NUDIX5 to generate nuclear ATP. The nuclear source of ATP is essential for hormone-induced chromatin remodeling, transcriptional regulation, and cell proliferation. Authors: Roni H. G. Wright, Antonios Lioutas, Francois Le Dily, Daniel Soronellas, Andy Pohl, Jaume Bonet, A. S. Nacht, Sara Samino, Jofre Font-Mateu, Guillermo P. Vicent, Michael Wierer, Miriam A. Trabado, Constanze Schelhorn, Carlo Carolis, Maria J. Macias, Oscar Yanes, Baldo Oliva, Miguel Beato