How to slow down aging and overcome cancer: An interview with Olga Lavrik.

— Your laboratory studies the processes of repair—specifically, how various damages are fixed in DNA—correct?

— Yes, and it's a very interesting, remarkable problem, I would say: understanding why certain enzymes are responsible for "repairing" DNA damage. They differ for various types of damage: how does the cell or the enzyme itself know when it is needed? How does the enzyme understand when to activate and begin the repair? How can the process be slowed down or accelerated?

— So, does that mean you need to study each of these enzymes? Is that what you are doing?

— No, not quite. I have always been interested in enzymes that operate not alone but within complex supramolecular assemblies, alongside other enzymes and protein factors—I have always been fascinated by enzymatic machines. This is much more interesting than observing a single enzyme.

— What a beautiful metaphor—enzymatic machines.

— But they really do work in harmony, just like machines! When some damage occurs due to internal or external factors, for example, due to oxidative stress (the presence of reactive oxygen species in the cell), a specific protein immediately recognizes this and rushes to the site of the "break" to repair it. Once the damage is fixed, another issue may arise, such as a DNA chain break, and a different enzyme that is capable of addressing that specific damage comes into play. Different parts of the machine work both sequentially and together in organized protein complexes. We know which enzymes can repair what, but other protein factors then regulate the process, either speeding it up or slowing it down at various stages—can you imagine? We are eagerly studying all of this.

— You mentioned that you have always been attracted to complex assemblies; does that go back to your school days? How did you become a scientist?

— I graduated from high school in Barnaul, in the Altai Krai: there were no opportunities to become a researcher; we only had a polytechnic institute, while the Novosibirsk State University was established in Akademgorodok at that time, and I had no doubts that I should enroll there to pursue science. I am, generally speaking, a chemist by education and have been interested in chemistry since school.

— I thought you were a biologist; did chemistry have any competition in your interests?

— Perhaps astronomy; I even attended an astronomy club, but I feel that astronomy lacks dynamics: you look through a telescope, searching for something, recording data. Chemistry suited my temperament better, and I was very lucky with my chemistry teacher. Additionally, I read popular science magazines that my mother subscribed to, such as "Chemistry and Life." The more complex the articles, the more interesting they were to me. There were articles on molecular biology, which was already developing at that time; I thought, how fascinating—chemistry in a living cell! I realized that chemical reactions also occur there, and in one of the articles, I read that reactions are accelerated by special catalysts—enzymes, but it was unknown how everything actually happened.

— Wow, so it turns out you became interested in chemical processes in cells back in school and are still studying them!

— It's not just an interest; I would say it's an emotional interest. The more I understand what I am researching, the more positive emotions I have about it: I am amazed and captivated by how everything works! The main thing in a scientist's work is interest. You sit at the computer or chat in the lab with colleagues, and suddenly a new idea comes to you. Ideas can come at any moment, and that is a great joy! Most of my new ideas come to me when I am walking home in the evening. Or an idea might unexpectedly strike during a vacation. Does that mean you are always thinking about work? Perhaps, but only about those aspects that emotionally occupy you. You can think about it in any situation because it is interesting. It's not like pondering, "I need to write a grant application."

— You trained as a chemist and then came to work at a biological institute?

— After graduating from university, I immediately entered graduate school, and my supervisor was the founder of the Institute of Bioorganic Chemistry (now the Institute of Chemical Biology and Fundamental Medicine), Academician Dmitry Georgievich Knorre. I was very fortunate to work with brilliant scientists; for example, my first course project was supervised by Lev Stepanovich Sandakhchiev, the creator of the scientific center for virology and biotechnology "Vector." It was a very strong scientific school, and the team was very supportive and eager to help if any difficulties arose. My passion for science intensified in such an environment; we often had interesting scientific discussions, and this atmosphere allowed me to grow as a scientist.

— Besides science, was there anything else that captivated you or still captivates you?

— I am involved in ballroom dancing, which I love very much, but my husband is the leader in our pair. He introduced me to dancing back in the 1970s; I learned the basic movements from the European ballroom dance program and even trained at the legendary "Spin" club, led by Gennady Borisovich Malkov. It so happened that I would leave dancing and then return because I worked a lot abroad, while Nikolai Lvovich continued to train. Now we attend dance classes together at the ballroom dance club for graduates of NSU. I decided that it was more important for me to perfect what I know rather than learn new variations, so we chose this club: there is almost no focus on learning new steps, making the classes fun and interesting for everyone.

— Is your husband also a scientist?

— Yes, he is a leading researcher at the V. V. Voevodsky Institute of Chemical Kinetics and Combustion.

— Does he support you in your work?

— Absolutely, otherwise I would not have been able to accomplish what I have in life—all of it has been with his support and patience, which has been long-standing. We have not collaborated scientifically; we could not organize that somehow, as we share different common interests—culture: we go to the theater, dance, and we raised a daughter—who is also a scientist, a chemist, a doctor of sciences, and a professor.

— Shall we return to enzymatic machines? If we don’t study enzymes separately, what should we study to understand how everything works?

— I started with individual enzymes, but I have always had a desire for increasing complexity. How did we initially conduct our research? We selected a model DNA structure with pre-existing damage, then studied individual enzymes and gradually observed how the DNA damage was repaired. Now I am interested in a different model that is closer to how things actually happen in the cell. The functioning of enzymes is influenced by their environment, so we need to look at DNA not in isolation but, if possible, within cellular structures. Such a structure is chromatin in the cell nucleus, where, besides DNA, there are also proteins known as histones. DNA and histones form the basic unit of chromatin—a nucleosome. It is at the nucleosome level that we are currently studying how the repair machines work. We have discovered that repair proteins interact at this structural level: they are as if pre-assembled in a complex, ready to react. It is assumed that when DNA damage occurs, the repair protein complex reorganizes instantly, and the proteins that can specifically repair that damage move to the site of injury. The most intriguing fundamental task now is to understand how the signal about DNA damage is transmitted in the nucleus and how the subsequent reorganization of the protein machines responsible for repair occurs.

— What have scientists discovered as the most important aspect of this process recently?

— In the broader context, I have not mentioned the main molecule that forms the basis of the regulators of the repair system. When damage occurs, a special signaling polymer is synthesized—a negatively charged, fairly long molecule of poly(ADP-ribose), or as it is called—the third nucleic acid. This polymer is synthesized on the DNA damage site by the enzyme poly(ADP-ribose) polymerase 1 (PARP1). For a long time, it was thought that it only served signaling functions, but my colleagues and I have discovered that PARP1 and poly(ADP-ribose) also participate in creating a specific non-membrane structure that gathers damaged DNA and repair proteins into a unified system. This creates a complex similar to a compartment. This allows for local concentration of repair proteins, enhancing the overall process's efficiency. Studying such structures is a promising direction, and this idea has captured the entire scientific community. We want to observe this process, but already in chromatin, in the supramolecular complex—that is the goal we have set from the perspective of fundamental research. The study of DNA repair is pursued in two ways: on one hand—at the cellular level (we are engaged in this as well), and on the other—through reconstructing the operation of complex repair machines using biochemical methods: here, experiments with damaged