Breakthrough in DNA Repair Mechanism Unveiled by University of Oxford and NTU Singapore Research

Strategic Insights -

A team of researchers from the University of Oxford and Nanyang Technological University, Singapore (NTU Singapore) has made a groundbreaking discovery in the field of DNA repair, revealing the mechanism by which cells identify and repair highly toxic DNA damage that causes cancer, neurodegeneration, and premature ageing. The study, published in Nucleic Acids Research, has significant implications for improving cancer therapy and healthy ageing.

The research team, led by Kristijan Ramadan, Toh Kian Chui Distinguished Professor in Cancer and Stem Cell Biology at the Lee Kong Chian School of Medicine, NTU Singapore, and Honorary Senior Researcher at the Department of Oncology, University of Oxford, has identified a new region within the SPRTN enzyme that enables it to selectively target DNA-protein crosslinks (DPCs), a type of DNA lesion induced by chemotherapy, formaldehyde, and UV exposure. This region, which detects chains of ubiquitin, allows SPRTN to rapidly increase its repair activity by 67-fold, clearing DPC lesions while sparing surrounding structures.

This discovery is crucial for protecting genome integrity and preventing diseases caused by DPC lesions. The research team emphasizes the importance of understanding how these lesions are repaired, as mutations in the SPRTN gene are associated with Ruijs-Aalfs syndrome, a rare condition characterized by chromosomal instability, premature ageing, and a high risk of early-onset liver cancer.

Key Takeaways:

  • The SPRTN enzyme has a newly discovered region that enables it to selectively target DNA-protein crosslinks (DPCs), a type of DNA lesion induced by chemotherapy, formaldehyde, and UV exposure.
  • This region detects chains of ubiquitin, allowing SPRTN to rapidly increase its repair activity by 67-fold, clearing DPC lesions while sparing surrounding structures.
  • The study has significant implications for improving cancer therapy and healthy ageing, as DPC lesions can cause neurodegeneration, premature ageing, and cancer.
  • Mutations in the SPRTN gene are associated with Ruijs-Aalfs syndrome, a rare condition characterized by chromosomal instability, premature ageing, and a high risk of early-onset liver cancer.
  • The discovery provides essential insights into our cells' natural defences and how defects in DPC repair can drive disease.
  • The researchers believe that this study lays the groundwork for developing potential ways to strengthen the body's defences against age-related diseases, as well as reduce the side effects of cancer therapies that damage DNA.

Statistics:

  • 67-fold increase in SPRTN repair activity when targeting DPC lesions
  • The SPRTN enzyme is slow and inefficient in repairing DPC lesions without ubiquitin chains
  • Longer chains of ubiquitin significantly accelerate the repair process
  • The study has implications for improving cancer therapy and healthy ageing

Sources:

  • Nucleic Acids Research
  • University of Oxford
  • Nanyang Technological University, Singapore (NTU Singapore)
  • Lee Kong Chian School of Medicine, NTU Singapore
  • Department of Oncology, University of Oxford
  • Tan Tock Seng Hospital, Singapore
  • NewsRx LLC (2025)