12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      A conserved NAD + binding pocket that regulates protein-protein interactions during aging

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD + (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD + to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate–ribose) polymerase], a critical DNA repair protein. As mice age and NAD + concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD +. Thus, NAD + directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.

          Related collections

          Author and article information

          Journal
          0404511
          7473
          Science
          Science
          Science (New York, N.Y.)
          0036-8075
          1095-9203
          12 April 2017
          24 March 2017
          24 March 2018
          : 355
          : 6331
          : 1312-1317
          Affiliations
          [1 ]Department of Genetics, Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA
          [2 ]Department of Biochemistry, University of Bayreuth, 95440 Bayreuth, Germany
          [3 ]National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
          [4 ]Division of Oncology Research, Department of Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA
          [5 ]Division of Biology, 434 Hutchinson Hall, River Campus, University of Rochester, Rochester, NY 14627, USA
          [6 ]Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales 2052, Australia
          Author notes
          []Corresponding author. david_sinclair@ 123456hms.harvard.edu
          [*]

          Present address: Department of Biology, St. Louis University, St. Louis, MO 63103, USA.

          [†]

          Present address: Department of Pharmacology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.

          Article
          PMC5456119 PMC5456119 5456119 nihpa863155
          10.1126/science.aad8242
          5456119
          28336669
          4bfef942-632e-46cb-8e68-fb96015a8cf2
          History
          Categories
          Article

          Comments

          Comment on this article