Science News from research organizations Hidden metabolism found operating inside the cell nucleus Scientists discovered hundreds of metabolic enzymes sitting on human DNA, revealing a hidden metabolism inside the cell nucleus that could shape cancer behavior. Date: March 9, 2026 Source: Center for Genomic Regulation Summary: Researchers have found hundreds of metabolic enzymes attached to human DNA inside the cell nucleus. Different tissues and cancers show unique patterns of these enzymes, forming a “nuclear metabolic fingerprint.” Some of the enzymes gather around damaged DNA to assist with repair. The discovery reveals an unexpected link between metabolism and gene regulation that could influence how cancers grow and respond to treatment. Share: Facebook Twitter Pinterest LinkedIN Email FULL STORY Breast cancers (left) show higher nuclear levels of energy-producing enzymes than lung cancers (right), revealing tissue-specific nuclear metabolism. Credit: Alberto Coll Manzano/Centro de Regulación Genómica A new study published in Nature Communications has revealed that more than 200 metabolic enzymes can be found directly on human DNA. Many of these enzymes are typically known for producing energy in mitochondria, yet researchers discovered them sitting on chromatin inside the cell nucleus. The study shows that different cell types, tissues, and cancers each display their own distinctive arrangement of metabolic enzymes within the nucleus. These enzymes interact with DNA in patterns that researchers describe as a "nuclear metabolic fingerprint," marking the first evidence that human cells may carry such unique nuclear signatures. Scientists still need to determine the precise role these enzymes play in the nucleus. They could be driving chemical reactions, influencing whether genes are switched on or off, or contributing to structural support. Even so, the findings already provide new insights into how tumors develop, adapt, and sometimes resist therapy. "Many of these enzymes synthesize essential building blocks of life, and their nuclear localization is associated with DNA repair. Their presence in the nucleus may therefore directly shape how cancer cells respond to genotoxic stress, a hallmark of many chemotherapeutic treatments. It's an entirely new world to explore," says Dr. Sara Sdelci, corresponding author of the study and researcher at the Centre for Genomic Regulation. Studying Proteins Bound to Chromatin To identify these enzymes, the research team used a technique that isolates proteins physically attached to chromatin, the natural packaging of DNA in human cells. Using this approach, they examined 44 cancer cell lines and 10 healthy cell types collected from ten different tissues. Metabolism and genome regulation have traditionally been viewed as largely separate biological systems. The nucleus houses the genome, while metabolic enzymes normally produce energy in mitochondria and the cytoplasm. Because of this assumption, the scale of the discovery surprised the researchers. They found that metabolic enzymes appear to play active roles in nuclear biology. About 7 percent of all proteins attached to chromatin turned out to be metabolic enzymes. This observation suggests that the nucleus may operate its own small metabolic network described by the researchers as a 'mini metabolism'. Unexpected Energy Pathways Inside the Nucleus Some of the enzymes detected were particularly surprising. The team identified proteins involved in oxidative phosphorylation, the cellular process responsible for generating most of a cell's energy, as regular occupants of the nucleus. The pattern of these enzymes also varied depending on cancer type. Oxidative phosphorylation enzymes were commonly observed in breast cancer cells but were largely missing in lung cancer cells. When scientists examined tumor samples taken directly from patients, they observed the same trend, confirming that nuclear metabolism varies depending on tissue type and disease. "We've been treating metabolism and genome regulation as two separate universes, but our work suggests they're talking to each other, and cancer cells might be exploiting these conversations to survive," says Dr. Savvas Kourtis, first author of the study. Enzymes Move to Damaged DNA The researchers also performed experiments to understand what these nuclear enzymes actually do. They focused on a group of enzymes responsible for producing molecules needed for DNA synthesis and repair. Their experiments showed that these enzymes gather near chromatin when DNA damage occurs. By concentrating in these regions, they appear to assist with repairing the genome. The team also discovered that the function of an enzyme can depend on its location inside the cell. One enzyme, called IMPDH2, behaved differently depending on where it was located. When researchers forced it to remain inside the nucleus, it helped maintain genome stability. When the same enzym