A GROUNDBREAKING study has uncovered a new class of DNA lesions that persist in human stem cells for months to years, contributing significantly to the mutation burden in somatic cells. Researchers analysed DNA samples from 89 donors, focusing on stem cells from blood, liver, and bronchial epithelium. They identified 818 DNA lesions that remained in cells over multiple cycles, with some persisting for over two years.
The study, which included high-resolution phylogenetic trees, found that these persistent lesions were more prevalent in individuals exposed to tobacco smoke or chemotherapy, highlighting the role of exogenous mutagens. In haematopoietic stem cells, lesions linked to endogenous sources were observed to persist steadily throughout a person’s life, including in utero, and showed a unique mutational signature (SBS19).
One of the most significant findings was that these persistent lesions were not only long-lasting but also actively contributed to the development of mutations. On average, a haematopoietic stem cell carries about eight such lesions at any given time, with half of them leading to mutations during each cell cycle. The study suggests that about 16% of mutations in blood cells are associated with this mutational signature, which is also commonly found in blood cancers.
This research sheds light on the complexity of DNA damage and its long-term effects, offering new insights into the origins of mutations and the potential risks posed by both internal and external sources of DNA damage.
Helena Bradbury, EMJ
Reference
Chapman MS et al. Prolonged persistence of mutagenic DNA lesions in somatic cells. Nature. 2025;doi: 10.1038/s41586-024-08423-8.
