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

Gilbert Richarme (1, 2) , Cailing Liu (3) , Mouadh Mihoub (1) , Jad Abdallah (4, 1) , Leger Thibaut (1) , Nicolas Joly (1, 5) , Jean-Claude Liebart (1) , Ula V. Jurkunas (3) , Marc Nadal (1) , Philippe Bouloc (6, 7) , Julien Dairou (2) , Aazdine Lamouri (8)

1 IJM (UMR_7592) - Institut Jacques Monod
2 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques
3 Massachusetts Eye and Ear Infirmary (affiliated with Harvard Medical School)
4 LAU - Lebanese American University
5 Max Planck Institute for the Science of Light
6 I2BC - Institut de Biologie Intégrative de la Cellule
7 SRRB - Signalisation et Réseaux de Régulations Bactériens
8 ITODYS (UMR_7086) - Interfaces, Traitements, Organisation et Dynamique des Systèmes

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.

Domains: Life Sciences [q-bio]

Gilbert Richarme, Cailing Liu, Mouadh Mihoub, Jad Abdallah, Leger Thibaut, et al.. Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science, 2017, 357 (6347), pp.208-211. ⟨10.1126/science.aag1095⟩. ⟨cea-01588317⟩