2. Academic Validation
  3. Guanine glycation repair by DJ-1/Park7 and its bacterial homologs

Guanine glycation repair by DJ-1/Park7 and its bacterial homologs

  • Science. 2017 Jul 14;357(6347):208-211. doi: 10.1126/science.aag1095.
Gilbert Richarme 1 2,  Cailing Liu 3,  Mouadh Mihoub 4,  Jad Abdallah 4 5,  Thibaut Leger 6,  Nicolas Joly 7,  Jean-Claude Liebart 4,  Ula V Jurkunas 3,  Marc Nadal 8,  Philippe Bouloc 9,  Julien Dairou 2,  Aazdine Lamouri 10
Affiliations

Affiliations

  • 1 Stress Molecules, Institut Jacques Monod, Université Paris Diderot-UMR7592, 15 rue Hélène Brion, 75013 Paris, France. [email protected].
  • 2 Chimie et Biochimie Pharmacologiques et Toxicologiques, Université Paris Descartes-Sorbonne Paris Cité, UMR 8601, 75270 Paris, France.
  • 3 Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
  • 4 Stress Molecules, Institut Jacques Monod, Université Paris Diderot-UMR7592, 15 rue Hélène Brion, 75013 Paris, France.
  • 5 School of Pharmacy, Lebanese American University, Byblos, 2038 1401 Lebanon.
  • 6 Proteomics Facility, Institut Jacques Monod, Université Paris Diderot-UMR7592, 75013 Paris, France.
  • 7 Cellular Cycle and Development, Institut Jacques Monod, Université Paris Diderot-UMR7592, 75013 Paris, France.
  • 8 Institut Jacques Monod, CNRS-Université Paris Diderot-UMR7592, 75013 Paris, France.
  • 9 Institute for Integrative Biology of the Cell (I2BC), Commissariat à l'Energie Atomique et aux Energies Alternatives, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
  • 10 Interfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS), Université Paris Diderot, UMR 7086, 15 rue J.-A. de Baïf, 75013 Paris, France.
PMID: 28596309 DOI: 10.1126/science.aag1095
Abstract

DNA damage induced by reactive carbonyls (mainly methylglyoxal and glyoxal), called DNA glycation, is quantitatively as important as oxidative damage. DNA glycation is associated with increased mutation frequency, DNA strand breaks, and cytotoxicity. However, in contrast to guanine oxidation repair, how glycated DNA is repaired remains undetermined. Here, we found that the parkinsonism-associated protein DJ-1 and its Bacterial homologs Hsp31, YhbO, and YajL could repair methylglyoxal- and glyoxal-glycated nucleotides and nucleic acids. DJ-1-depleted cells displayed increased levels of glycated DNA, DNA strand breaks, and phosphorylated p53. Deglycase-deficient Bacterial mutants displayed increased levels of glycated DNA and RNA and exhibited strong mutator phenotypes. Thus, DJ-1 and its prokaryotic homologs constitute a major nucleotide repair system that we name guanine glycation repair.

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