19 November 2017
Hero protein rescues sugar-damaged DNA
Published online 21 June 2017
A DNA repair protein could be a new therapeutic target for diseases like atherosclerosis and retinopathy.
Researchers have uncovered a mechanism that repairs DNA damaged by sugar metabolism byproducts.
When these sugar molecules accumulate in cells, they can bind to DNA nucleotides, particularly guanosine and deoxyguanosine. This process, called glycation, damages DNA and leads to increased frequency of mutation, DNA strand breaks, and cytotoxicity.
The researchers investigated the potential role of a protein, called DJ-1, in repairing glycated nucleotides. The protein was already known for its involvement in repairing other proteins by acting as a ‘deglycase’.
“We showed that DJ-1 acts as a ‘nucleotide sanitizer’ that repairs nucleotides before their conversion to advanced glycation end-products, which lead to irreversible damage,” says biochemist Jad Abdallah of the Lebanese American University, one of the study’s co-authors. “We also showed that DJ-1 performs direct repair of DNA and RNA, and its depletion in cells leads to increased DNA glycation and fragmentation.”
DJ-1 deglycases could represent the only enzymes that repair both proteins and nucleic acids, the researchers conclude in their study in Science1.
The team next hopes to correlate this discovery with clinical research, says Abdallah. Glycation is responsible for arterial stiffening, contractile dysfunction in the heart, scarring of the kidney’s tiny blood vessels, aggregation of proteins in the lens of the eye, and damage to the eye’s blood vessels. DJ-1 could therefore play an important role in treating diseases like atherosclerosis, hypertension, cardiomyopathy, nephropathy, cataracts, and retinopathy, explains Abdallah.
- Richarme, G. et al. Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science http://dx.doi.org/10.1126/scienceaaag1095 (2017).