Stress Molecules, Institut Jacques Monod, Université Paris Diderot-UMR7592, 15 rue Hélène Brion, 75013 Paris, France.
Chimie et Biochimie Pharmacologiques et Toxicologiques, Université Paris Descartes-Sorbonne Paris Cité, UMR 8601, 75270 Paris, France.
Science. 2017 Jul 14;357(6347):208-211. doi: 10.1126/science.aag1095. Epub 2017 Jun 8.
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.
活性羰基化合物（主要是甲基乙二醛和乙二醛）引起的 DNA 损伤，称为 DNA 糖化，其数量与氧化损伤一样重要。DNA 糖化与突变频率增加、DNA 链断裂和细胞毒性有关。然而，与鸟嘌呤氧化修复不同，糖化 DNA 如何被修复仍未确定。在这里，我们发现帕金森病相关蛋白 DJ-1 及其细菌同源物 Hsp31、YhbO 和 YajL 可以修复甲基乙二醛和乙二醛糖化核苷酸和核酸。DJ-1 耗尽的细胞显示出更高水平的糖化 DNA、DNA 链断裂和磷酸化的 p53。去糖基化酶缺陷的细菌突变体显示出更高水平的糖化 DNA 和 RNA，并表现出强烈的突变表型。因此，DJ-1 和其原核同源物构成了一个主要的核苷酸修复系统，我们称之为鸟嘌呤糖化修复。
