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鶹ýվ researchers contribute to international study on DNA synthesis

A study published in Science reveals how a single protein helps cells decide when to produce the building blocks of DNA — a discovery with potential implications for treatments of cancer and inherited metabolic disorders

Inside every cell, a finely tuned metabolic network determines when to build, recycle, or stop producing essential molecules. A central part of this network is folate metabolism, which provides vital chemical units for the synthesis of DNA, RNA and amino acids. When this system is disturbed – through genetic mutations or a lack of dietary folates – the consequences can range from developmental disorders to cancer.

Now, researchers from , the Research Center for Molecular Medicine of the Austrian Academy of Sciences, together with collaborators from the University of Oxford and contributors from The Research Institute of the 鶹ýվ Health Centre (The Institute), have identified an unexpected player in this metabolic balance: the enzyme NUDT5.

The study, published in , shows that NUDT5 helps switch off purine production—the pathway that generates the building blocks of DNA—but does so without using its enzymatic activity. Instead, the protein acts as a kind of molecular scaffold that physically restrains a key biosynthetic step when purine levels are already high.

“We were delighted to play a role in this important work, by providing cultured cells from patients with mutations in the MTHFD1 gene,” said , one of the study’s co-authors and a Scientist in the  at The Institute. “Cells from patients with a genetic disease, which we , were critical in showing that adenosine can also be toxic depending on the exact nature of the MTHFD1ܳٲپDz.”

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