DNA repair as a way to cure cancer

Our DNA is capable of self-repair thanks to a number of complex molecular mechanisms, which are crucial for ensuring genomic stability, but also for preventing the onset of diseases caused by damage to genetic material, first and foremost cancer. The project ‘Mechanism of DNA Double-Strand Break Repair and its Regulation’, led by Prof. Petr Cejka, Full Professor at the Faculty of Biomedical Sciences and Group Leader at the Institute for Research in Biomedicine (IRB), using advanced biochemical approaches, aims to clarify how cells decide which repair pathway to activate, with important implications for personalised medicine and genetic engineering.

This project is one of ten USI projects that won an SNSF grant.

Professor Cejka, what are the possible risks if DNA is damaged?

If DNA damage is not repaired correctly, (a) damage can either persist or (b) repaired incorrectly. Damaged DNA can cause problems during cellular division (even impossibility to divide and cell death), or it can interfere with normal cellular function. Incorrect repair leads to mutations, with the risk of cancer and aging.

Why is it important to know the mechanisms that guide cells' choice of repair pathway?

One of the hallmarks of cancer is accumulation of mutations and defects in DNA repair. If we know how cells repair DNA, we can also understand how defects lead to cancer. Oftentimes , paradoxically, inhibition of DNA repair or DNA damage is used in cancer treatment (including radiotherapy)

When it comes to therapies involving the manipulation of genetic material there is often much mistrust, can you explain how the approaches you develop are safe and why there are no risks to patient safety?

Approaches in which DNA is repaired are in the very early stages, and as you point out must be strictly regulated. To date, these manipulations have been used to cure very serious disorders, in which the pathogenic mutation is well known, and it is obvious which correction must be made. Other applications are ethically problematic and therefore inadmissible. The probability of introducing additional mutations theoretically may exist, but the probability will be low, and is balanced against enormous benefit (in most cases, life saving) resulting from the wanted correction.