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Laboratory for Transcription Regulation and Replication

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As of 30.01.2020

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scientific publications
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General information

Name of the project: Eukaryotic transcription: mechanisms of epigenetic processes and development of regulators for bioengineering

Strategy for Scientific and Technological Development Priority Level: в

Goals and objectives

Research directions: Research of transcription regulation, research of action of targeted medication in the context of chromatin

Project objective: Research of mechanisms of genetic and epigenetic processes and development of regulators for bioengineering

The practical value of the study

  • We have proposer research of the mechanism of chromatin transcription that is called «nucleosome cycle»: nucleosomes are not only preserved on DNA but are also returned to the initial location in case of disconnection.
  • It has been found that the key role in stabilization of histones is played by allosteric effects based on influence of electrons, atoms and the environment as a whole.
  • We have found an ATP-independent chromatin remodeling using the FACT protein, the main part of modification of histones runs with consumption of energy stored in ATP. Another object – PARP – can also change the structure of chromatin, even though its impact is not as that of FACT.

Implemented results of research:

  • Patent of the Russian Federation No. 497950 of 10 November 2013 (Authors: Vasiliy M. Studitsky, Olga I. Studitskaya) «A method for testing substances affecting the process of aging» opens a new way of usage of special functional nucleosome matrices for assessment of impact of medications that are able to affect the process of cell aging.
  • Patent of the Russian Federation No. 2580006 of 14 October 2016 (Authors: Vasiliy M. Studitsky, Olga I. Studitskaya, Alexey K. Shaitan) «A method for screening of potential anti-tumor inhibitor preparation FACT» can be used for screening chemical compounds, predominantly of the new class of anti-tumor substances aimed at inhibition of action of FACT relying on usage of methods of molecular docking testing agents with molecular functional surfaces FACT.
  • Patent of the Russian Federation No. 2639535 of 14 June 2017 (Authors: Vasiliy M. Studitsky, Olga I. Studitskaya, Yelena Yu. Kotova, Nataliya V. Malyuchenko) «A method of screening anti-tumor medications - inhibitors of PARP1 based on biochemical methods of analysis» reveals a method of screening of anti-tumor medications - inhibitors of PARP1. To implement this method it is needed to assemble nucleosomes from cleaned refined histones on DNA matrices then doping with RNA polymerase and deposition of a molecular target - the PARP1 protein - to the produced complex with subsequent introduction of a transcription buffer as well as tested chemical compounds.
  • Patent of the Russian Federation No. 2649767 of 04 April 2018 (Authors: Vasiliy M. Studitsky, Alexey V. Feofanov, Daniel Ch. Sultanov, Kseniya S. Kudryashova, Nadezhda S. Gerasimova, Nataliya V. Malyuchenko) «A test-system from screening chemical compounds for presence of inhibition activity with respect to PARP-1» presents a method of for screening chemical compounds for presence of inhibition activity with respect to PARP-1. The method relies on FRET-microscopy of single particles (spFRET) that is a mixture including a mononucleosome complex on a nucleosome-positioning DNA matrix tagged with a pair of fluorophores forming donor-acceptor pairs for implementing the FRET effect, the PARP-1 protein and its substrate- NAD+.

Education and career development:

  • 4 candidate dissertations, 6 doctoral dissertations, 6 undergraduate theses have been defended.
  • Three lecture have been compiled: «Histone chaperones», «Mechanisms of interactions of chromatin-remodeling proteins», «Epigenetic mechanisms and transcription regulation».
  • We have prepared 5 practical problems as part of development of the «Big case stud» for bachelor and master degree students of the Department of Bioengineering of the Faculty of Biology of the Moscow State University.
  • Five internships have been organized at the Laboratory for professionals of other organizations.

Collaborations: Fox Chase Cancer Center (USA): joint research, student exchange

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McCullough L.L., Connell Z., Xin H., Studitsky V.M., Feofanov A.V., Valieva M.E., Formosa T.
Functional Roles of the DNA-binding HMGB Domain in the Histone Chaperone FACT in Nucleosome Reorganization. The Journal of Biological Chemistry 293(16): 6121–6133 (2018)
Valieva M.E., Gerasimova N.S., Kudryashova K.S., Kozlova A.L., Kirpichnikov M.P., Hu Q., Botuyan M.V., Mer G., Feofanov A.V., Studitsky V.M.
Stabilization of Nucleosomes by Histone Tails and by FACT Revealed by spFRET Microscopy. Cancers (Basel) 9(1): 3 (2017)
Valieva M.E., Armeev G.A., Kudryashova K.S., Gerasimova N.S., Shaytan A.K., Kulaeva O.I., McCullough L.L., Formosa T., Georgiev P.G., Kirpichnikov M.P., Studitsky V.M., Feofanov A.V.
Large-scale ATP-independent Nucleosome Unfolding by a Histone Chaperone. Nature Structural & Molecular Biology 23(12): 1111–1116 (2016)
Chang H.W., Pandey M., Kulaeva O.I., Patel S.S., Studitsky V.M.
Overcoming a Nucleosomal Barrier to Replication. Science Advances 2(11): e1601865 (2016)
Gerasimova N.S., Pestov N.A., Kulaeva O.I., Clark D.J., Studitsky V.M.
Transcription-induced DNA Supercoiling: New Roles of Intranucleosomal DNA Loops in DNA Repair and Transcription. Transcription 7(3): 91–95 (2016)
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