DNA-protein cross-links promote cGAS-STING–driven premature aging and embryonic lethality

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Source: Science Magazine

Original: https://www.science.org/doi/abs/10.1126/science.adx9445?af=R...

Published: 2026-01-29T08:00:00Z

DNA-protein cross-links (DPKs) are serious DNA damages that occur during chemotherapy, exposure to formaldehyde and ultraviolet radiation and prevent the copying of the genetic material of cells[4]. A research team from the University of Oxford and Nanyang Technological University discovered a mechanism by which the enzyme SPRTN recognizes and repairs these damages by degrading proteins bound to DNA[4]. A study showed that longer ubiquitin chains (protein tags) significantly accelerate DPK repair compared to shorter chains, allowing SPRTN to act rapidly and selectively[4]. Mutations in the SPRTN gene cause Ruijs-Aalfs syndrome, a rare disease characterized by chromosomal instability, premature aging, and a high risk of liver cancer at an early age[4]. These insights into DPK repair have important implications for the development of new ways to strengthen the body's defenses against aging-related diseases and reduce the side effects of chemotherapy[4].