Turning DNA functions on and off with light

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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 instruction manual found in every cell. Biochemists from the University of Munster have now developed a strategy to control the biological functions of DNA with the help of light. This enables researchers to better understand and control the processes occurring in the cell – for example, major chemical changes and regulatory levers in DNA. The results have been published in the journal Angvende Chemi.

The functions of the cell depend on the enzyme. Enzymes are proteins that cause chemical reactions in the cell. They help synthesize metabolic products, make copies of DNA molecules, convert energy to the cell’s activities, transform DNA indigenously and break down certain molecules. A team of researchers, led by Professor Andrea Rentminster of the Institute of Biochemistry at the University of Munster, used a so-called enzymatic cascade reaction to better understand and track these functions. This sequence of sequential reaction steps involving various enzymes makes it possible to transfer so-called photocaging groups — chemical groups that can be removed to the DNA via radiation with light. Previously, studies had shown that only small residues (small modifications such as methyl groups) could be selectively localized to DNA, RNA (ribonucleic acid) or proteins.

“As a result of our work, it is now possible to transfer large residues or modifications such as the photocaging groups just mentioned,” explains Neil Kloecker, one of the study’s lead authors and Ph.D. Students in the Institute of Biochemistry. Structural Biologist Proc. Working closely with Daniel Kummel, who also works at the Institute of Biochemistry, it was also possible to elucidate the basis of altered activity at the molecular level.

Using so-called protein engineering, a method for which a Nobel Prize was awarded in 2018, Munster researchers engineered an enzyme in the cascade, making it possible to switch on and off DNA functions through light. With the aid of protein design, it was possible to expand the substrate spectrum of enzymes – in this case, methionine adenosyltransferase (MATS). In their work, the researchers investigated two MATs. The modifications made provide a starting point for developing other MATs with a broader substrate spectrum. Andries Rentmister states, “Combining these MATs with other enzymes has potential for future cellular applications. This is an important step in epigenetic studies to apply in-situ generated, non-natural substances to other enzymes. ”

Enzymatic Photocaging for the Study of Gene Regulation via DNA Methylation

more information:
Freideriki Michailidou et al, Maikigeschneiderte SAM het Synthetasen zur enzymatischen Herstellung von AdoMet oga Analoga mit Photoschutzgruppen und zur revuriblen DNA ask in Kaskadenreaktionen – Modifizierung. Angvende Chemi (2020). DOI: 10.1002 / ange.202012623

Provided by the University of Munster

Quotes: Switching DNA functions with Prakash (2020, 29 December) Retrieved from https://phys.org/news/2020-12-dna-functions.html as of 30 December 2020.

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