Prof. Marcin Nowotny from the International Institute of Molecular and Cell Biology in Warsaw, Poland, received the 2021 FNP Prize in the area of life and earth sciences for the explanation of the molecular mechanisms of DNA damage recognition and its repair.

Marcin Nowotny was born in Warsaw in 1973. He graduated from the Faculty of Chemistry at the University of Warsaw in 1998. He received his Ph.D. degree in 2002 from the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw, and his habilitation eleven years later from the Institute of Biochemistry and Biophysics of the Polish Academy of Sciences in Warsaw. He received full professorship in 2020.

From 2003 to 2008, Nowotny worked at the National Institutes of Health in Bethesda, USA. In 2008, after winning an international competition, he became head of the Laboratory of Protein Structure at the International Institute of Molecular and Cell Biology in Warsaw, Poland.

Nowotny?s scientific achievements have received much recognition. His most important awards and honors include the Prime Minister?s Dissertation Award (2003), the EMBO Installation Grant (2003), the Howard Hughes Medical Institute Early Career Scientist Award (2012), the Knight?s Cross of the Order of Polonia Restituta (2013), and the Academia Europaea Burgen Scholarship (2013). In March 2020, together with eighteen partners from Europe, Nowotny received the Exscalate4CoV grant from Horizon 2020 to search for effective therapy against the SARS-CoV-2 virus. Besides his scientific activities, Nowotny is also involved in the organization of science in Poland. From 2018 to 2020, he served as a member and then chairman of the Science Policy Committee under the Minister of Science and Higher Education. Moreover, Nowotny holds membership in many international scientific societies, such as Academia Europaea and the European Molecular Biology Organization. He won several FNP programmes: START, Ideas for Poland, Conference Stipends, and TEAM.

Nowotny?s research focuses on the relationship between the structure and function of proteins that process nucleic acids: DNA and RNA. These are the proteins that participate in the synthesis, processing, and maintenance of nucleic acids stability.

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Prof. Marcin Nowotny is a highly respected international scientist whose work crucially contributes to the understanding of the molecular mechanisms of DNA damage and its repair. He received the 2022 FNP Prize for his research in this area.

During the life of an organism, its genetic material encoded in DNA undergoes various types of damage. This happens both during cell division and due to various environmental factors, such as ultraviolet radiation or harmful chemicals. Each cell develops many thousands of such defects every day. Hence, the cells are equipped with complex and extremely precise repair mechanisms that continuously recognize and repair damage to DNA. Otherwise, errors accumulating in the structure of nucleic acids would prevent the smooth functioning of cells and, consequently, that of tissues, organs, and entire organisms. Defects in DNA repair, and the resulting DNA instability, are one of the reasons for the formation and development of cancer, neurodegenerative diseases, as well as aging.

Nowotny has described the structure, characterized the function, and explained the mechanism of several proteins and protein complexes key in cell biology, which interact with nucleic acids and participate in DNA repair. The results of his work have been described in several highly cited scientific journals.

One group of enzymes involved in DNA repair described by Nowotny are resolvases, which are proteins involved in one of the DNA repair pathways: the homologous recombination of DNA. An important process occurring in the cells of all DNA-containing organisms ? from viruses to humans ? homologous recombination involves the exchange of certain DNA fragments between two similar molecules of this acid. Homologous recombination is a universal, ubiquitous mechanism used by cells to e.g. accurately repair breaks in both DNA strands, which are extremely dangerous to the cell. To fulfill its purpose, homologous recombination must be accurate or cause no mutations. Nowotny has studied and described the structure and function of a bacterial resolvase called RuvC, which is involved in homologous recombination. This research allowed scientists to understand the mechanism of the RuvC enzyme, which consists in coordinating notches in DNA strands.

Other proteins described by Nowotny and involved in DNA repair include nucleases (enzymes that cut the DNA strand) named SLX1 and Rad2. These are enzymes that work in eukaryotic cells, which also include human cells. The Rad2 nuclease cuts the damaged DNA fragment. Nowotny?s list of studies on enzymes interacting with DNA in various genome repair pathways does not end there: the number and range of the proteins he characterized are impressive.

In his endeavor to determine the structure of proteins and their complexes in DNA, Nowotny employs the latest biochemical methodologies combined with X-ray crystallography and, more recently, cryogenic electron microscopy (cryo-EM).

Research into how DNA repair proteins work not only increases our understanding of what happens inside cells but is also of great practical importance. Since DNA damage contributes to the formation and development of cancers and neurodegenerative diseases, among other illnesses, proteins that repair this damage and maintain genome stability could become targets for creating drugs effective in treating these diseases. On the other hand, we know that cancer cells have disrupted DNA repair mechanisms, making them more sensitive to DNA damage, with which they cannot cope and die. Many of the currently used anticancer drugs damage DNA, thus leading to the death of cancer cells. The ability to block repair mechanisms in cancer cells even more strongly would increase the effectiveness of cancer drugs. This is a relatively new concept and a promising avenue for the development of anticancer drugs, for which Prof. Marcin Nowotny?s research provides a perfect contribution.

 

Photo: Magdalena Wiśniewska-Krasińska_FNP Archives

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