Scientists discovered a new way that cells control the production of purines, which are building blocks your body needs to make DNA and RNA. They found that a protein called NUDT5 acts like a brake on purine production when there’s already enough in the cell. This discovery was made by studying how cells respond to problems with folate metabolism, a key process in your body. The findings could help explain why some cancer treatments work and why certain genetic conditions cause problems. This research was published in the prestigious journal Science and represents an important step in understanding how cells manage their own building materials.

The Quick Take

  • What they studied: How a protein called NUDT5 controls whether cells make more purines (building blocks for DNA), and what happens when this control system breaks down
  • Who participated: This was laboratory research using cell cultures and genetic models rather than human volunteers. Scientists studied cells with different genetic changes to understand how NUDT5 works
  • Key finding: NUDT5 works like a brake on purine production by physically connecting to another protein called PPAT. When cells have enough purines, NUDT5 slows down production. When NUDT5 is missing, cells make too many purines and become resistant to certain cancer drugs
  • What it means for you: This discovery may eventually help doctors improve cancer treatments and understand rare genetic diseases better. However, this is basic laboratory research, and it will take years of additional study before these findings could affect medical treatments

The Research Details

Scientists started by studying cells with mutations in a gene called MTHFD1, which is involved in folate metabolism—a process that helps cells make DNA. They noticed these cells had problems making purines properly. To understand why, they investigated a protein called NUDT5 that seemed to be involved in this process.

The researchers used two main approaches: genetic depletion (turning off the NUDT5 gene) and chemical degradation (using drugs to break down the NUDT5 protein). Both methods produced the same result, suggesting NUDT5 was important for controlling purine production. They then studied how NUDT5 physically interacts with PPAT, the main enzyme that starts purine production, to understand the mechanism.

Understanding how cells control purine production is important because purines are essential for making DNA and RNA—the genetic material cells need to survive and divide. Cancer cells often need more purines than normal cells, which is why some cancer drugs target purine production. By discovering how NUDT5 acts as a brake on this process, scientists can better understand why cancer cells sometimes become resistant to these drugs and how to potentially overcome that resistance.

This research was published in Science, one of the world’s most prestigious scientific journals, which means it underwent rigorous peer review. The study used multiple experimental approaches (genetic and chemical) that confirmed the same findings, which strengthens confidence in the results. However, this is laboratory research using cells and genetic models, not human studies, so the findings need further validation before clinical applications

What the Results Show

The main discovery was that NUDT5 acts as a control switch for purine production. When researchers removed NUDT5 from cells, purine production increased significantly. Importantly, the researchers found that NUDT5 doesn’t work by using its enzymatic activity (its chemical-cutting ability). Instead, NUDT5 works by physically attaching to PPAT, the enzyme that starts purine production, and holding it back.

This finding was surprising because NUDT5 is known as a hydrolase, meaning scientists expected it to work by breaking down molecules. Instead, it works more like a brake pad—it needs to be present and in contact with PPAT to slow things down. When NUDT5 is missing, PPAT works without restraint, producing too many purines.

The research revealed two important practical consequences of losing NUDT5 function. First, cancer cells without NUDT5 became resistant to purine analog drugs—medications used to treat certain cancers. This explains why some cancer treatments stop working and suggests that NUDT5 status might be important for predicting which patients will respond to these drugs. Second, in cells with MTHFD1 deficiency (a rare genetic condition), losing NUDT5 prevented adenosine toxicity, a dangerous buildup of a purine-related molecule that can harm cells. This suggests NUDT5 might be a target for treating certain genetic diseases.

Previous research showed that folate metabolism and purine production are connected, but the exact mechanism wasn’t clear. This study fills that gap by identifying NUDT5 as a specific link between these two processes. The finding that NUDT5 works through a scaffolding role (acting as a physical connector) rather than through enzymatic activity is novel and changes how scientists think about this protein’s function. This discovery also provides new insight into why some cancer treatments fail, building on decades of research into cancer drug resistance.

This research was conducted entirely in laboratory cell cultures and genetic models, not in living organisms or humans. The findings need to be confirmed in animal studies and eventually human research before they can be applied to medical treatment. Additionally, the study focused on one specific pathway in cells, and it’s unclear how NUDT5 might affect other cellular processes. The research also doesn’t explain all the details of how NUDT5 and PPAT interact or how other factors might influence this control system

The Bottom Line

At this stage, there are no direct recommendations for patients or the general public. This is fundamental research that advances our understanding of cell biology. For researchers and pharmaceutical companies, this finding suggests that NUDT5 could be a target for developing new cancer treatments or therapies for genetic diseases involving purine metabolism. The confidence level is moderate—the laboratory findings are solid, but clinical applications are years away

Cancer researchers and drug developers should pay attention to this finding, as it may help explain drug resistance and suggest new treatment strategies. Doctors who treat patients with MTHFD1 deficiency or other rare genetic conditions affecting purine metabolism should follow future research in this area. The general public should be aware that this type of basic research is essential for developing better treatments, but shouldn’t expect immediate medical applications

This is early-stage research. It typically takes 5-10 years or more for laboratory discoveries to lead to clinical trials, and another 5-10 years for potential FDA approval of new treatments. Patients shouldn’t expect any direct medical applications from this research for at least a decade, but the knowledge gained could eventually lead to better cancer treatments or therapies for rare genetic diseases

Want to Apply This Research?

  • While this research doesn’t directly apply to personal health tracking yet, users interested in cancer prevention or genetic health could track factors known to affect purine metabolism: daily folate intake (leafy greens, legumes), hydration levels, and exercise frequency. These factors support overall cellular health and DNA synthesis
  • Users could implement a tracking habit for folate-rich foods, since folate metabolism is directly connected to purine production. This includes tracking servings of spinach, kale, lentils, chickpeas, and asparagus. While this won’t directly affect NUDT5 function, supporting healthy folate metabolism supports overall cellular health
  • Create a weekly nutrition log tracking folate intake and overall diet quality. Users with family history of genetic conditions affecting purine metabolism should discuss this research with their healthcare provider and track any relevant symptoms or health markers their doctor recommends. For cancer patients on purine analog drugs, discuss NUDT5 status with oncologists as this research develops into clinical applications

This article describes laboratory research that has not yet been tested in humans. The findings are preliminary and represent basic science discoveries rather than clinical recommendations. This research should not be used to make decisions about cancer treatment, genetic testing, or any medical condition without consulting a qualified healthcare provider. If you have a family history of genetic disorders affecting purine metabolism or are undergoing cancer treatment, discuss this research with your doctor to understand how it might relate to your specific situation. Always consult with medical professionals before making any health-related decisions based on scientific research.