![]() The anti-cancer drugs curaxins target spatial genome organization. Kantidze OL, Luzhin AV, Nizovtseva EV, Safina A, Valieva ME, Golov AK, Velichko AK, Lyubitelev AV, Feofanov AV, Gurova KV, Studitsky VM, Razin SV. ![]() The 3D Genome as a Target for Anticancer Therapy. Kantidze OL, Gurova KV, Studitsky VM, Razin SV. International journal of molecular sciences. Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine. Nilov D, Maluchenko N, Kurgina T, Pushkarev S, Lys A, Kutuzov M, Gerasimova N, Feofanov A, Svedas V, Lavrik O, Studitsky VM. Maluchenko N.V., Nilov D.K., Pushkarev S.V., Kotova E.Y., Gerasimova N.S., Kirpichnikov M.P., Langelier M.F., Pascal J.M., Akhtar M.S., Feofanov A.V., Studitsky V.M., Mechanisms of nucleosome reorganization by parp1. Sivkina A.L., Karlova M.G., Valieva M.E., McCullough L.L., Formosa T., Shaytan A.K., Feofanov A.V., Kirpichnikov M.P., Sokolova O.S., Studitsky V.M., Electron microscopy analysis of atp-independent nucleosome unfolding by fact. This simple experimental system allowed us to identify elements of chromatin structure and protein factors involved in distant gene regulation. Our research focuses on the following critical questions: What features of DNA/chromatin template allow efficient communication over a distance? What are distinct features of the regulatory elements that are capable of action over a distance? We have adopted relatively simple, highly purified and efficient experimental systems for quantitative analysis of enhancer action over a distance in vitro. The most recent focus of our studies is on the mechanism of action of histone chaperones FACT & PARP1 during Pol II transcription.ĭistant regulation of gene transcription initiation is mediated by direct interaction between proteins bound at communicating DNA elements and involves looping of intervening DNA/chromatin regions. These features of the mechanism suggest that it is likely used for maintenance of chromatin structure and the “histone code”. Using this system, we have discovered a novel mechanism involving survival of core histones and their modifications without even transient histone dissociation from DNA. ![]() This system faithfully recapitulates numerous features of transcribed chromatin described in vivo and allows their molecular analysis in vitro. In early 2000 we have established a “minimal” experimental system that maintains transcription through various defined mono- and polynucleosomes by RNA polymerase II. ![]() The questions are: Can the differences in affinity be explained by the chromatin context of the binding sites? What changes in chromatin structure are involved in p53-DNA interaction? We are trying to understand the mechanisms of interaction of p53 with its binding sites in chromatin. It has an apparent high affinity to the response elements regulating cell cycle arrest genes (CCA-sites) and a lower affinity to the sites associated with apoptosis (Apo-sites) in vivo. Tumor suppressor p53 is a sequence-specific DNA-binding protein, possibly a pioneering factor involved in gene regulation. Our research focuses on the following questions: What changes in chromatin structure are involved in the reorganization? How do various anti-cancer drugs affect this process? What are the mechanisms of trapping of the histone chaperones in chromatin? Recently we have studied the mechanisms of FACT- and PARP1-dependent chromatin reorganization. Importantly, both hFACT & hPARP1 are involved in carcinogenesis and are important targets for anti-cancer drugs. The mechanisms of gene regulation over a distance (by enhancers & insulators).įACT and PARP1 are histone chaperones that can increase chromatin accessibility to various proteins during initiation and elongation of transcription. The mechanisms and regulation of transcript elongation through chromatin by RNA polymerase II, and 4. Mechanisms of interaction of sequence-specific regulator proteins (e.g. Mechanisms of histone chaperones FACT and PARP1 action during transcription and its regulation. Currently our efforts are focused in the following primary directions: 1. This goal will be achieved using a combination of molecular genetics, genomics, biochemical, single-particle, structural and computational modeling approaches. The major research goal in my laboratory is to understand the molecular mechanisms and regulation of the vital process of eukaryotic transcription in chromatin, and the role of the factors involved in cancer development and human aging (e.g. Regulation of gene expression occurs primarily at the initial step (transcription) and involves DNA sequences, protein factors and dynamic changes in structure of DNA-protein complexes (chromatin). Development and functioning of higher organisms critically depends on properly regulated gene expression.
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