You are currently viewing the abstract.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
Register for free to read this article
As a service to the community, this article is available for free. Existing users log in.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
A nuclear power source in the cell
DNA is packaged onto nucleosomes, the principal component of chromatin. This chromatin must be remodeled to allow gene transcription, DNA replication, and DNA repair machineries access to the enclosed DNA. Chromatin-remodeling complexes require high levels of cellular energy to do their job. Wright et al. show that the energy needed to remodel chromatin can be derived from a source, poly-ADP-ribose, in the cell nucleus, rather than by diffusion of ATP from mitochondria in the cytoplasm, the usual powerhouse of the cell. Poly-ADP-ribose is converted to ADP-ribose and then to ATP, which can be used to fuel chromatin remodeling within the nucleus.
Science, this issue p. 1221
Abstract
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.
