Switch DNA functions on and off with light

DNA is the basis of life on Earth. The function of DNA is to store all the genetic information that an organism needs to develop, function and reproduce. It is essentially a biological manual found in every cell. Biochemists at the University of Münster have now developed a strategy to control the biological functions of DNA with the help of light. This allows researchers to better understand and control the processes that take place in the cell – for example, epigenetics, the main chemical change and regulatory leverage in the DNA. The results have been published in the journal applied chemistry.

The functions of the cell depend on enzymes. Enzymes are proteins that carry out chemical reactions in the cell. They help synthesize metabolic products, make copies of the DNA molecules, convert energy for the cell’s activities, epigenetically alter the DNA and break down certain molecules. A team of researchers led by Prof. Andrea Rentmeister of the Institute for Biochemistry at the University of Münster used a so-called enzymatic cascade reaction to better understand and monitor these functions. This sequence of successive reaction steps involving different enzymes makes it possible to transfer so-called photocaging groups – chemical groups that can be removed by irradiation with light – to DNA. Previously, studies had shown that only small residues (minor modifications such as methyl groups) could be selectively transferred to DNA, RNA (ribonucleic acid) or proteins.

“As a result of our work, it is now possible to transfer larger residues or modifications, such as the photocaging groups just mentioned,” explains Nils Klöcker, one of the study’s lead authors and a Ph.D. student at the Institute of Biochemistry. In collaboration with structural biologist Prof. Daniel Kümmel, who also works at the Institute for Biochemistry, it was also possible to explain the basis for the altered activity at the molecular level.

Using so-called protein engineering, a method for which a Nobel Prize was awarded in 2018, the Münster researchers have constructed one enzyme in the cascade, which makes it possible to switch DNA functions on and off with light. Protein design made it possible to expand the substrate spectrum of enzymes – in this case methionine adenosyl transferases (MATs). In their work, the researchers looked at two MATs. The modifications made provide a starting point for the development of other MATs with an extensive substrate spectrum. “Combining these MATs with other enzymes has potential for future cellular applications. This is an important step in implementing in-situ generated, non-natural compounds for other enzymes in epigenetic studies,” says Andrea Rentmeister.