Not-so-sweet DNA damage repaired Glyoxal and methylglyoxal, by-products of sugar metabolism that are present in all cells, can react with, and thus damage, DNA. Indeed, glycation of guanine (G) is as prevalent as the major product of oxidative damage in DNA, 8-oxo-dG. Richarme et al. show that both prokaryotes and eukaryotes have dedicated systems that specifically repair glycation damage (see the Perspective by Dingler and Patel). The parkinsonism-associated protein DJ-1/Park7 and its bacterial homologs Hsp31, YhbO, and YajL direct the enzymatic repair of damaged glycated bases in DNA. The proteins also clean up the more vulnerable pool of free nucleotides in the cell, which are more susceptible to glycation than the nucleotides within DNA. Science, this issue p. 208; see also p. 130 A DNA repair system acts specifically on bases damaged by reaction with by-products of sugar metabolism in the cell. 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.

中文翻译：

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DJ-1/Park7 及其细菌同源物修复鸟嘌呤糖化

不那么甜的 DNA 损伤修复 乙二醛和甲基乙二醛是存在于所有细胞中的糖代谢副产物，可以与 DNA 发生反应，从而破坏 DNA。事实上，鸟嘌呤 (G) 的糖基化与 DNA 氧化损伤的主要产物 8-oxo-dG 一样普遍。理查姆等人。表明原核生物和真核生物都有专门修复糖基化损伤的专用系统（参见 Dingler 和 Patel 的观点）。帕金森病相关蛋白 DJ-1/Park7 及其细菌同源物 Hsp31、YhbO 和 YajL 指导 DNA 中受损糖化碱基的酶促修复。这些蛋白质还可以清除细胞中更脆弱的游离核苷酸库，它们比 DNA 中的核苷酸更容易发生糖化。科学，这个问题 p。208; 另见第。130 DNA 修复系统专门作用于因与细胞中糖代谢副产物反应而受​​损的碱基。由反应性羰基化合物（主要是甲基乙二醛和乙二醛）诱导的 DNA 损伤，称为 DNA 糖基化，在数量上与氧化损伤一样重要。DNA 糖基化与增加的突变频率、DNA 链断裂和细胞毒性有关。然而，与鸟嘌呤氧化修复相反，糖化 DNA 的修复方式仍未确定。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 耗尽的细胞显示出糖化 DNA、DNA 链断裂和磷酸化 p53 水平增加。缺乏脱糖酶的细菌突变体显示出糖化 DNA 和 RNA 水平增加，并表现出强烈的增变表型。因此，DJ-1 及其原核同源物构成了一个主要的核苷酸修复系统，我们将其命名为鸟嘌呤糖基化修复。