‘My dream is to be able to see how the cell’s entire repair machine works’
How do cells protect our DNA from damage? Professor of Human Genetics Martijn Luijsterburg studies how DNA repair offers insight into fundamental biological processes that are important to the diagnosis and treatment of hereditary disorders.
What is the core message of your inaugural lecture, and why did you choose this?
‘Our DNA sustains damage every day. For our health, cells must be able to recognise and repair this damage. I explain this using the metaphor of a genetic railway track.
‘RNA polymerase is a kind of train that travels along the DNA. This train reads the genetic information and converts it into messenger RNA (mRNA), enabling cells to do their job.
‘Sometimes the train encounters damage in the DNA and cannot proceed. This can cause serious problems, such as cancer, ageing and nervous system diseases. Learning more about how cells protect and repair their DNA will help us understand how our bodies work. It can also help improve diagnoses and develop new treatments for hereditary diseases.’
What main research lines do you and your team focus on?
‘Our main research is on what happens when RNA polymerase comes up against damaged DNA. Over the past ten years, we’ve discovered several new repair proteins that help with this, including ELOF1 and STK19. These play a key role in removing stalled RNA polymerase and repairing DNA damage. We’re also investigating how other proteins that travel alongside RNA polymerase as it reads the DNA help protect the genetic material.
‘A second aspect of our research is studying the structure of the entire repair complex. To do so, we use advanced techniques such as cryo-electron microscopy, which allow us to examine molecules in great detail. This helps us understand how cells protect our DNA and what goes wrong in hereditary diseases where DNA damage is not repaired properly.’
What role do teaching and patient care play in your vision for this field?
‘Through our teaching, we can explain complex biological processes to students and young researchers. Teaching also forces me to keep returning to the fundamental concepts of the field. That, in turn, helps me in my research.
‘In patient care, we work with patient organisations in the Netherlands and other countries. We advise on hereditary diseases in which DNA damage is not properly repaired and also assist clinical geneticists by testing patient cells for research purposes, so they can make the correct diagnosis. We work closely with clinical geneticists around the world, which means that discoveries from basic research can help improve patient care and speed up the identification of rare disorders.’
What stands out most from the past few years?
‘That basic research can completely change our understanding of a biological process.
‘When my research group first started, we knew very little about the proteins that help when RNA polymerase stalls while reading DNA. By developing new techniques and combining different research methods, we discovered several new repair proteins. We also now know in detail the sequence in which these proteins work together to repair DNA damage.
‘That moment when the puzzle pieces come together to form a coherent mechanism is a special one. It shows that significant progress often results not from a single spectacular discovery, but from years of patiently developing fundamental knowledge that ultimately delivers an entirely new insight.
‘It’s also struck me how important collaboration is in this process. These discoveries are the result of a close-knit team of researchers tackling complex questions together. The enthusiasm, the shared quest for answers and the feeling that, as a group, you are solving a scientific puzzle step by step: this is what makes research not only successful but also deeply inspiring.’
How do patients and society benefit from your work?
‘Our research focuses on the fundamentals of how cells work, but that doesn’t mean it’s not important to society. If we can understand how DNA damage can lead to disease, we can help develop new ways to diagnose and potentially treat diseases.
‘For example, our research has led to the discovery of new genetic diseases caused by DNA not being repaired properly. It has also contributed to treatment recommendations for patients with ERCC1 gene mutations.
‘Our knowledge also helps doctors identify rare conditions more quickly and accurately. This is important because it ensures patients receive the right care sooner. Our work demonstrates that basic scientific research not only produces new knowledge but can contribute to better care and medical innovations.’
Looking ahead, where do you hope the field will be in 10 to 15 years?
‘I hope that we’ll have a more or less complete understanding of how reading genes, DNA damage and DNA repair are interconnected. Many of the processes we’re studying were only recently discovered. That’s why there are so many questions we still need to answer.
‘My dream is to be able to see how the cell’s entire molecular repair machinery works and how all the proteins involved work together to keep our DNA fit and healthy. This is crucial to the medicine of the future. The better we understand how cells function, age and become diseased, the greater the chance we’ll find new ways to prevent, detect and treat diseases.’
Martijn Luijsterburg’s inaugural lecture, ‘The Vulnerable Code: On Obstacles on the Genetic Track’, was held on 6 July.