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

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Science  14 Jul 2017:
Vol. 357, Issue 6347, pp. 208-211
DOI: 10.1126/science.aag1095

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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


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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