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“In practice what we’re doing is hacking into a cell so that we can reverse its wiring and enable it to focus on maintaining its DNA”, SINTEF researcher Torkild Visnes says.

Research into disease prevention instead uncovers a method of repairing DNA

Researchers have discovered a new method of activating enzymes that may make it possible to repair proteins that have been damaged as a result of hereditary diseases, such as some types of skin cancer.

Communications Director
Presented by: SINTEF
Published

A standard approach to treating disease is to prevent biological functions from damaging the body’s tissues. This is normally done by introducing molecules that bond with harmful proteins.

This approach was being investigated by an international team of researchers aiming to use an enzyme to prevent the development of infectious disease. However, instead of blocking the infection, the researchers discovered that the enzyme they were studying was very active. So, it was given a new function – and the cell began to adopt a new way of maintaining its DNA.

Published in Science

“In simple terms, we tried to disable a lock by putting chewing gum in it, only to find that instead of jamming the lock, the door opened wide”, says SINTEF researcher Torkild Visnes, who works in the fields of biotechnology and nanomedicine, and is part of the team of researchers.

The team’s discovery has now been published in the research periodical Science. The article describes how the researchers first discovered, and then developed and characterised, the effect of a new organic molecule that can activate a new function in a targeted protein. The protein acts to maintain DNA in human cells.

Great potential

“We now have the knowledge and methods needed to search for and design other molecules that have similar effects on other proteins of interest”, says Visnes . “This may offer us new opportunities to modify enzymatic processes. In practice, this means that we can introduce new chemical and biological functions into cells and do so in a variety of different contexts. What is especially exciting is that we may be able to introduce chemical reactions that would otherwise not occur naturally."

This work is the result of an international collaboration with partners in Sweden, Spain, Germany and the UK. Work in Norway has been carried out by SINTEF Industry and SINTEF Ocean. The researchers are currently working to develop new applications of their discovery.

“We will now be using our new knowledge to activate other enzymes”, says Visnes. “This may involve proteins and may have impacts on key medical issues such as hereditary diseases. For example, we can envisage reactivating damaged proteins that have mutated and resulted in hereditary diseases. There are also major industrial applications. We may be able to activate key industrial proteins and enzymes and give them new functions, enabling them to become more effective and carry out tasks that are currently not possible."

Researchers from the SINTEF research team are among the co-authors of the scientific article. Torkild Visnes, Antonio Sarno, Simon Loevenich and Hanne Haslene-Hox have contributed by measuring how human cells repair oxidised DNA in the presence both of the recently developed molecule and known inhibitors (drugs that are used to suppress infection and pain). This has been a key experiment, designed to characterise and understand how the new molecule impacts on cells.

Facts about enzymes

  • Enzymes are substances, primarily proteins, that catalyse the chemical processes that take place in living organisms. They facilitate chemical reactions without themselves being consumed in the reactions.
  • Enzymes make it possible for cells to extract energy from nutrients, generate energy from fats and carbohydrates, and construct all the components that make up living cells, including the enzymes themselves. Chemically speaking, life can be seen as the result of a controlled system of collaborative, enzyme-catalysed reactions. As many as three thousand enzymes have been described.

(Source: the Norwegian encyclopaedia (Store norske leksikon))

Reference:

Michel et al. 'Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function', Science, vol. 376, 2022. DOI: 10.1126/science.abf8980 Abstract.

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