ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling

Science. 2016 Jun 3;352(6290):1221-5. doi: 10.1126/science.aad9335.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism*
  • Adenosine Triphosphate / biosynthesis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Cell Proliferation
  • Chromatin Assembly and Disassembly*
  • Crystallography, X-Ray
  • Diphosphates / metabolism
  • Energy Metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Hydrolysis
  • MCF-7 Cells
  • Poly (ADP-Ribose) Polymerase-1
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Progestins / metabolism*
  • Progestins / pharmacology
  • Protein Multimerization
  • Pyrophosphatases / chemistry
  • Pyrophosphatases / genetics
  • Pyrophosphatases / metabolism*


  • Diphosphates
  • Progestins
  • Adenosine Diphosphate Ribose
  • Poly Adenosine Diphosphate Ribose
  • diphosphoric acid
  • Adenosine Triphosphate
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • NUDT5 protein, human
  • Pyrophosphatases