Researchers part funded by Breast Cancer Now have uncovered how our cells repair a harmful type of DNA damage. Their findings shed new light on how healthy cells protect themselves from harm and could help guide future work to improve cancer treatments.
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In research published earlier this year, Professor Kristijan Ramadan and his team at the University of Oxford revealed the unique role of a key molecule in DNA damage repair, called SPRTN.
The researchers’ work has improved our understanding of how cancer can develop, and laid the groundwork for finding new ways to make treatments kinder and more effective.
Why this type of DNA damage matters
Every cell in our body contains DNA, the instruction manual for making every protein that our cells need to grow and survive. But everyday processes in the body, chemicals in our environment, and some cancer treatments like chemotherapy can damage our DNA.
Most of the time, our cells are very good at repairing this damage, allowing us to stay healthy. However, in some cases, proteins can become physically stuck to the DNA, causing a blockage that prevents the cell from easily reading or copying DNA in that section. We call this type of damage a DNA-protein crosslink (DPC).
These DPCs can increase the risk of healthy cells developing into cancer. So, cells need to be able to recognise and repair these crosslinks quickly and accurately.
Because of this, Kristijan and his team wanted to understand how cells remove these proteins without harming themselves in the process.
Searching for a signal
One key molecule involved in repairing these crosslinks is called SPRTN. SPRTN acts like a pair of scissors that cuts the protein away from the DNA. It’s a crucial part of the repair process, and without it, harmful crosslinks would pile up.
However, SPRTN has to work very carefully. Proteins are attached to DNA all the time as part of normal cell activity. If SPRTN cut the wrong protein away, it could damage important processes the cell needs to survive.
Kristijan and his team discovered that SPRTN looks for a tiny, simple molecular signal on damaged proteins - a tag called ubiquitin. When damaged proteins build up a chain of these tags, SPRTN recognises this as a distress signal.
The team showed that when SPRTN detects these ubiquitin chains, it becomes significantly more active. And importantly, it ignores proteins that don’t carry this distress signal.
The researchers also uncovered new details about how SPRTN attaches to these ubiquitin chains. They identified a previously unknown region of SPRTN that helps it bind to the tagged proteins more strongly. This dual-binding ability is what gives SPRTN the precision it needs to focus only on the proteins that pose a threat.
What this means for people with breast cancer
This research is an important step forward in understanding how healthy cells respond to DNA damage. Because some breast cancer treatments deliberately create DNA–protein crosslinks to kill cancer cells, knowing exactly how the body repairs them could help scientists find new ways to improve these treatments.
While this work is still at an early stage, it provides a strong foundation for developing future treatment strategies. It also helps explain how cells protect themselves from cancer developing, opening the door for more research into how to prevent cancer.
This research was part-funded by Breast Cancer Now and published in Nucleic Acids Research
Smarter, kinder treatments
Without research, there won’t be change. That’s why our scientists are discovering how to develop better treatments. So that one day, no one dies from breast cancer.