Laboratory of Bioorganic Chemistry of Enzymes

Olga I. Lavrik,
Full Member of RAS, D.Chem.Sci.

Phone: +7(383) 363-51-95, Email

• USSR State Prize Winner (1984)
• Winner of the D.I. Mendeleev All-Union Chemical Society Prize (1988)
• Winner of the Prize of SB RAS (1985, 1986, 1988, 1990 years)
• Fellow of State Scholarship for Outstanding Scientists of Russia (1994–2000)
• Fellow of the George Soros Foundation – Honorary Professor (1994)
• Visiting Professor of University of Pierre and Marie Curie (Paris 6)
• Badge of Honor on the 115th anniversary of Novosibirsk (2008)
• The commemorative medal «For a Contribution to Development of the Novosibirsk Region» in honor of the 75 anniversary of region
• Winner of an award “Academina” (The woman in science) in honor of the 55 anniversary of SB RAS (2012)
• Certificate of Merit from the Rector of Novosibirsk State University (2013)
• Commander of the Order of Academic Palms, France (2016)
• Medal of the Order of Merit for the Fatherland, II degree (2018)
• Medal in memory of Academician N. M. Emanuel for achievements in the field of chemical and biochemical physics (2019).

• Investigation of the process of excisional repair of DNA bases in higher eukaryotes. Study of interactions between DNA polymerases beta, lambda, apurinic / apyrimidine endonuclease (APE1), flap endonuclease-1 (FEN1), PCNA, XRCC1, poly (ADP-riboso) polymerase-1 (PARP1) with DNA structures that mimic intermediates excisional repair of bases. Identification of new participants in base repair in cell extracts using the method of affinity modification in combination with MALDI-MS and the establishment of their functions.
• Study of the damage recognition process and mechanism of nucleotide excision repair system. Development of methods of NER process modulation for chemotherapy improvement. Study of repair mechanisms of clustered damages.
• Investigation of DNA synthesis through damage catalyzed by DNA polymerases beta, lambda, iota.
• Study of the mechanisms of multiple DNA damage repair.
• Search of new efficient inhibitors and regulators of key enzymes of DNA replication/repair systems as potential drugs in treatment of cancer and other human diseases.
• X-ray analysis of DNA repair proteins and their complexes with substrates.

• The main protein-protein interactions were revealed in the reparosome, which carries out the process of excisional repair of bases in the DNA structure damaged by oxidative stress and other influences [Moor et al., Nucleic Acids Res, 2015; Moor et al., Int J Mol Sci. 2020].
• New protein targets for poly (ADP-ribosyl) ation catalyzed by poly (ADP-ribose) polymerase 1 (PARP1) have been discovered, such as XPC-HR23B, a key protein for recognizing bulky DNA lesions, YB-1, a regulatory protein for transcription and granule formation cell stress, p-21 protein, OGG1 DNA glycosylase [Maltseva et al., J Biol Chem, 2015; Alemasova et al., Biochimie, 2015; Dutto, Sukhanova et al., PLoS One, 2016; Lebedeva et al, Front Cell Dev Biol. 2021].
• A fundamentally new function of enzymes of the PARP family (PARP1 / 2/3) has been discovered - the ability to carry out poly (ADP-ribosyl) ation of DNA in breaks [Talhaoui I. et al., Nucleic Acids Res, 2016; Zarkovic G, Belousova EA et al., Nucleic Acids Res, 2018; Belousova et al. Sci Rep. 2018].
• It was revealed that RNA / DNA-binding protein YB-1 is able to modulate PAR synthesis depending on the intensity of DNA damage, as well as to protect PAR from PARG hydrolysis, significantly prolonging the polymer lifetime, and, like histones or polyamines, to stimulate PARP1 activity and reduce the effectiveness of PARP1 inhibitors (Alemasova et al., Biochim Biophys Acta., 2016, Alemasova et al, Oncotarget, 2018; Naumenko et al., Biomolecules, 2020).
• Highly effective inhibitors of the important therapeutic target tyrosyl-DNA phosphodiesterase 1 have been developed as potential drugs. (Patent of the Russian Federation No. 2627764-Diploma from the Federal Service for Intellectual Property in the nomination 100 BEST INVENTIONS OF RUSSIA-2017)

1. Petruseva I.O., Naumenko N.V., Kuper J., Anarbayev R.O., Kappenberger J., Kisker C., Lavrik O.I. The Interaction Efficiency of XPD-p44 With Bulky DNA Damages Depends on the Structure of the Damage. Front. Cell Dev Biol. 2021. V. 9. P. 617160.
2. Rechkunova N.I., Krasikova Y.S., Lavrik O.I. Interactome of base and nucleotide excision DNA repair systems. Mol. Biol. (Mosk.) 2021. V. 55. N 2. P. 155-166.
3. Ilina E.S., Lavrik O.I., Khodyreva S.N. 5'-deoxyribose phosphate lyase activity of apurinic/apyrimidinic endonuclease 1. Mol. Biol. (Mosk.) 2021. V. 55 . N 2. P. 234-240.
4. Dyrkheeva N.S., Zakharenko A.L., Novoselova E.S., Chepanova A.A., Ryabchikova E.I., Lavrik O.I., Popova N.A., Nikolin V.P., Luzina O.A., Salakhutdinov N.F. Antitumor activity of the combination of topotecan and tyrosyl-DNA-phosphodiesterase 1 inhibitor on model krebs-2 mouse ascite carcinoma. Mol. Biol. (Mosk.) 2021. V. 55. N 2. P. 273-277.
5. Evdokimov A.N., Popov A.A., Ryabchikova E.I., Koval O.A., Romanenko S., Trifanov V.A., Petruseva I.O., Lavrik I.N., Lavrik O.I. Uncovering molecular mechanisms of regulated cell. death in the naked mole rat. Aging-US. 2021. V. 13. N 3. P. 3239-3253.
6. Kutuzov M.M., Belousova E.A., Kurgina T.A., Ukraintsev A.A., Vasil'eva I.A., Khodyreva S.N., Lavrik O.I. The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context. Scientific Reports. 2021. V. 11. N 1. P. 4849.
7. Derzhalova A.C., Markov O.V., Fokina A.A., Shiohama Y., Zatsepin T., Khodyreva S.N., Fujii M., Zenkova M.A., Stetsenko D.A. Novel Lipid-Oligonucleotide Conjugates Containing Long-Chain Sulfonyl Phosphoramidate Groups: Synthesis and Biological Properties. Applied Sciences (Basel). 2021 . V. 11 . N 3. P. 1-15.
8. Lebedeva N.A., Rechkunova N.I., Endutkin A.V., Lavrik O.I. Apurinic/Apyrimidinic Endonuclease 1 and Tyrosyl-DNA Phosphodiesterase 1 Prevent Suicidal Covalent DNA-Protein Crosslink at Apurinic/Apyrimidinic Site. Front. Cell Dev Biol. 2021. V. 8. P. 617301.
9. Gladkova E.D., Chepanova A.A., Ilina E.S., Zakharenko A.L., Reynisson J., Luzina O.A., Volcho К.P., Lavrik O.I., Salakhutdinov N.F. Discovery of Novel Sultone Fused Berberine Derivatives as Promising Tdp1 Inhibitors. Molecules. 2021. V. 26. N 7 P. 1945.
10. Vasil'eva I.A., Moor N.A., Anarbayev R.O., Kutuzov M.M., Lavrik O.I. Functional Roles of PARP2 in Assembling Protein–Protein Complexes Involved in Base Excision DNA Repair. Int. J. Mol. Sci. 2021. V. 22. P. 4679.
11. Salomatina O.V., Popadyuk I.I., Komarova N.I., Salakhutdinov N.F., Volcho К.P., Zakharenko A.L., Zakharova O., Chepanova A.A., Dyrkheeva N.S., Anarbayev R.O., Lavrik O.I., Reynisson J. Deoxycholic acid as a molecular scaffold for tyrosyl-DNA phosphodiesterase 1 inhibition: a synthesis, structure–activity relationship and molecular modeling study. Steroids. 2021. V. 165. С. 108771.
12. Krasikova Y.S., Rechkunova N.I., Lavrik O.I. Nucleotide excision repair: From molecular defects to neurological abnormalities. Int. J. Mol. Sci. 2021. V. 22. N 122 P. 6220.
13. Dyrkheeva N.S., Filimonov A.S., Luzina O.A., Zakharenko A.L., Ilina E.S., Malakhova A.A., Medvedev S.P., Reynisson J., Volcho К.P., Zakiyan S.M., Salakhutdinov N.F., Lavrik O.I. New hybrid compounds combining fragments of usnic acid and monoterpenoids for effective tyrosyl-dna phosphodiesterase 1 inhibition. Biomolecules. 2021. V. 11. N 7.P. 973.
14. Munkuev A.A., Mozhaitsev E.S., Chepanova A.A., Suslov E.V., Korchagina D.V., Zakharova O., Ilina E.S., Khodyreva S.N., Zakharenko A.L., Reynisson J., Volcho .P., Salakhutdinov N.F., Lavrik O.I. Novel tdp1 inhibitors based on adamantane connected with monoterpene moieties via heterocyclic fragments. Molecules. 2021. V. 26. N 111. P. 3128.
15. Savelyev N., Shepelev N.M., Lavrik O.I., Rubtsova M.P., Dontsova O.A. PARP1 Regulates the Biogenesis and Activity of Telomerase Complex Through Modification of H/ACA-Proteins. Front. Cell Dev Biol. 2021. V. 919. P. 621134.
16. Kovaleva K., Yarovaya O., Ponomarev K.Yu., Cheresiz S., Azimirrad A., Chernyshova I.A., Zakharenko A.L., Konev V., Khlebnikova T., Mozhaytsev E., Suslov E., Nilov D., Švedas V.K., Pokrovsky A., Lavrik O.I., Salakhutdinov N.F. Design, synthesis, and molecular docking study of new tyrosyl-dna phosphodiesterase 1 (Tdp1) inhibitors combining resin acids and adamantane moieties. Pharmaceuticals. 2021 . V. 14 . N 5. P. 422.
17. Moor N.A., Vasil'eva I.A., Kuznetsov N.A., Lavrik O.I. Human apurinic/apyrimidinic endonuclease 1 is modified in vitro by poly(ADP-ribose) polymerase 1 under control of the structure of damaged DNA. Biochimie. 2020. V. 168. P. 144-155.
18. Chepanova A.A., Li-Zhulanov N.S., Sukhikh A.S., Zafar A., Reynisson J., Zakharenko A.L., Zakharova O., Korchagina D.V., Volcho К.P., Salakhutdinov N.F., Lavrik O.I. Effective Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 Based on Monoterpenoids as Potential Agents for Antitumor Therapy. Биоорганическая химия. 2020 . V. 45. N 6. P. 647–655.
19. Mamontova E.M., Zakharenko A.L., Zakharova O., Dyrkheeva N.S., Volcho К.P., Reynisson J., Arabshahi H.J., Salakhutdinov N.F., Lavrik O.I. Identification of novel inhibitors for the tyrosyl-DNA-phosphodiesterase 1 (Tdp1) mutant SCAN1 using virtual screening. Bioorg. Med. Chem. 2020. V. 28. N 1. P. 115234.
20. Sherstyuk Y.V., Ivanisenko N.V., Zakharenko A.L., Sukhanova M.V., Peshkov R.Y., Eltsov I.V., Kutuzov M.M., Kurgina T.A., Belousova E.A., Ivanisenko V.A., Lavrik O.I., Silnikov V.N., Abramova T.V. Design, Synthesis and Molecular Modeling Study of Conjugates of ADP and Morpholino Nucleosides as A Novel Class of Inhibitors of PARP-1, PARP-2 and PARP-3. Int. J. Mol. Sci. 2020. V. 21. N 1.pii: E214.
21. Kretov D.A., Mordovkina D.A., Eliseeva I.A., Lyabin D.N., Polyakov D.N., Joshi V., Desforges B., Hamon L., Lavrik O.I., Pastre D., Curmi P.A., Ovchinnikova L.P. Inhibition of Transcription Induces Phosphorylation of YB-1 at Ser102 and Its Accumulation in the Nucleus. Cells. 2020. V. 9. N 1. E104.
22. Vasil'eva I.A., Moor N.A., Lavrik O.I. Effect of Human XRCC1 Protein Oxidation on the Functional Activity of Its Complexes with the Key Enzymes of DNA Base Excision Repair Biochemistry (Moscow). 2020. V. 85. N 3.P. 288 – 299.
23. Rechkunova N.I., Lavrik O.I. Photoreactive DNA as a Tool to Study Replication Protein A Functioning in DNA Replication and Repair. Photochemistry and Photobiology. 2020. V. 96. N 2. P. 440-449.
24. Moor N.A., Vasil'eva I.A., Lavrik O.I. Functional Role of N-Terminal Extension of Human AP Endonuclease 1 in Coordination of Base Excision DNA Repair via Protein–Protein Interactions. Int. J. Mol. Sci. 2020. V. 21. N 9. P. 3122.
25. Khodyreva S.N., Lavrik O.I. Non-canonical interaction of DNA repair proteins with intact and cleaved AP sites. DNA Repair. 2020. V. 90. P. 102847.
26. Yudkina A.V., Endutkin A.V., Dyatlova E., Moor N.A., Vokhtantsev I.P., Grin I.R., Zharkov D.O. Displacement of slow-turnover DNA glycosylases by molecular traffic on DNA Genes. 2020. V. 11. N 8. P. 866.
27. Il'ina I.V., Dyrkheeva N.S., Zakharenko A.L., Sidorenko A.Yu., Li-Zhulanov N., Korchagina D.V., Chand R., Ayine-Tora D.M., Chepanova A.A., Zakharova O., Ilina E.S., Reynisson J., Malakhova A.A., Medvedev S.P., Zakiyan S.M., Volcho К.P., Salakhutdinov N.F., Lavrik O.I. Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1. Molecules. 2020. V. 25. N 15. P. 3496.
28. Kovaleva K., Mamontova E.M., Yarovaya O., Zakharova O., Zakharenko A.L., Lavrik O.I., Salakhutdinov N.F. Dehydroabietylamine-based thiazolidin-4-ones and 2-thioxoimidazolidin-4-ones as novel tyrosyl-DNA phosphodiesterase 1 inhibitors. Molecular Diversity. 2020.
29. Gladkova E.D., Nechepurenko I.V., Bredikhin R.A., Chepanova A.A., Zakharenko A.L., Luzina O.A., Ilina E.S., Dyrkheeva N.S., Mamontova E.M., Anarbayev R.O., Reynisson J., Volcho К.P., Salakhutdinov N.F., Lavrik O.I. The first berberine-based inhibitors of tyrosyl-DNA phosphodiesterase 1 (Tdp1), an important DNA repair enzyme Int. J. Mol. Sci.. 2020 . V. 21 . P. 7162.
30. Sukhanova M.V., Singatulina A., Pastre D., Lavrik O.I.Fused in Sarcoma (FUS) in DNA Repair: Tango with Poly(ADP-ribose) Polymerase 1 and Compartmentalisation of Damaged DNA Int. J. Mol. Sci. 2020. V. 21. P. 7020.
31. Naumenko K.N., Sukhanova M.V., Hamon L, Kurgina T.A., Alemasova E.E., Kutuzov M.M., Pastre D., Lavrik O.I. Regulation of Poly(ADP-Ribose) Polymerase 1 Activity by Y-Box-Binding Protein 1. Biomolecules. 2020. V. 10. N 9. E1325.
32. Zakharenko A.L., Drenichev M.S., Dyrkheeva N.S., Ivanov G.A., Oslovsky V.E., Ilina E.S., Chernyshova I.A., Lavrik O.I., Mikhailov S.N. Inhibition of Tyrosyl-DNA Phosphodiesterase 1 by Lipophilic Pyrimidine Nucleosides. Molecules. 2020. V. 25. N 16. P. 3694.
33. Luzina O., Filimonov A., Zakharenko A.L., Chepanova A.A., Zakharova O., Ilina E.S., Dyrkheeva N.S., Likhatskaya G., Salakhutdinov N.F., Lavrik O.I. Usnic Acid Conjugates with Monoterpenoids as Potent Tyrosyl-DNA Phosphodiesterase 1 Inhibitors. Journal of Nat. Prod. 2020. V. 83. N 8. P. 2320-2329.
34. Kutuzov M.M., Belousova E.A., Ilina E.S., Lavrik O.I. Impact of PARP1, PARP2 & PARP3 on the Base Excision Repair of Nucleosomal DNA. Adv. Exp. Med. Biol. 2020. V. 1241. P. 47-57.
35. Nilov D., Maluchenko N., Kurgina T.A., Pushkarev S., Lys A., Kutuzov M.M., Gerasimova N., Feofanov A., Lavrik O.I., Studitsky V.M. Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine. Int. J. Mol. Sci. 2020. V. 21. N 6. P. 2159.
36. Dyrkheeva N.S., Anarbayev R.O., Lebedeva N.A., Kupryushkin M.S., Kuznetsova A.A., Kuznetsov N.A., Rechkunova N.I., Lavrik O.I. Human tyrosyl-DNA phosphodiesterase 1 possesses transphosphooligonucleotidation activity with primary alcohols. Front. Cell Dev Biol. 2020. V. 8. P. 604732.
37. Belenkaya S.V., Bondar A.A., Kurgina T.A., Elchaninov V.V., Bakulina A.Yu., Rukhlova E.A., Lavrik O.I., Ilyichev A.A., Shcherbakov D.N. Characterization of the Altai Maral Chymosin Gene, Production of a Chymosin Recombinant Analog in the Prokaryotic Expression System, and Analysis of Its Several Biochemical Properties. Biochemistry (Moscow). 2020. V. 85. N 7. P. 781-791.
38. Lavrik O.I. PARPs’ impact on base excision. DNA Repair. 2020. V.93. P. 102911.
39. Boldinova E.O., Belousova E.A., Gagarinskaya D.I., Maltseva E.A., Khodyreva S.N., Lavrik O.I., Makarova A.V. Strand Displacement Activity of PrimPol. Int. J. Mol. Sci. V. 21.P. 9027.

• Patent - No. 2384623 from 03.20.10- Ilyina E.S., Lavrik O.I., Khodyreva S.N. «Method for the detection of Ku antigen in extracts of human cells» Priority date 10.07.2008; Validity period Russia, 10.07.2028
• Patent - No. 2411948 dated 02.20.11 Lavrik O.I., Khodyreva S.N., Zakharenko A.L., Mikhailov S.N., Kulikova I.V., Efimtseva E.V. «Substance for inhibiting of human poly (ADP-ribose) polymerase 1.» Priority Date 10.19.2009; Validity period Russia, 10.19.2029.
• Patent - No. 2492242, dated 10.09.2013 Evdokimov A.N., Petruseva I.O., Tsidulko A.Yu., Koroleva L.S., Serpokrylova I.Yu., Silnikov V.N., Lavrik O. AND. A method for evaluating the activity of an excisional mammalian nucleotide repair system. Priority date 04.24.2012; Validity period Russia, 04.24.2032.
• Patent - No. 2500675, dated 10.12.2013 Zakharenko A.L., Sokolov D.N., Luzina O.A., Sukhanova M.V., Khodyreva S.N., Zakharova O.D., Salakhutdinov N. F., Lavrik O.I. Means for inhibiting of human poly (ADP-ribose) polymerase 1. Priority Date 09/18/2012; Validity period Russia, 09/18/2032.
• Patent - No. 2527457, dated August 27, 2014 Kurochkin N.N., Drenichev M.S., Timofeev E.N., Kolganova N.A., Tararov V.I., Zakharenko A.L., Khodyreva S. N., Lavrik O.I., Mikhailov S.N. Inhibitors of human poly (ADP-ribose) polymerase 1 based on uracil derivatives. Priority Date 09.27.2012; Validity period Russia, 09.27.2032.
• Patent - No. 2581060, Priority date of September 30, 2014 Khomenko T. M., Volcho K. P., Zakharenko A. L., Zhukova S. V., Anarbaev R. O., Lavrik O. I., Salakhutdinov N.F. Means for inhibiting of human tyrosyl DNA phosphodiesterase 1.
• Patent - No. 2605329, Priority date of 10/15/2015 Zakharenko A.L., Lebedeva N.A., Luzina O.A., Salakhutdinov N.F., Lavrik O.I. Means for inhibiting of human tyrosyl DNA phosphodiesterase 1. Validity period Russia, 10/15/2035
• Patent - No. 2612875, Priority date dated 12/14/2015, Khomenko T.M., Zakharenko A.L., Odarchenko T.I., Reinisson J., Volcho K.P., Lavrik O.I., Salakhutdinov N .F. «Substance for inhibiting of human tyrosyl DNA phosphodiesterase 1.»
• Patent - No. 2627764, Priority date 08/08/2016, Luzina O.A., Zakharenko A.L., Sokolov D.N., Salakhutdinov N.F., Lavrik O.I., Khazanov V.A. «2-Acetyl-6- (2- (2- (4-bromobenzylidene) hydrazinyl) thiazol-4-yl) -3, 7, 9-trihydroxy-8, 9b-dimethyldibenzo [b, d] furan-1 (9bH ) -one exhibiting an inhibitory effect on the human tyrosyl DNA phosphodiesterase 1».
• Patent - No. 2612256, Priority date 11/17/2015, Zakharenko A.L., Luzina O.A., Sokolov D.N., Rakhmanova M.E., Salakhutdinov N.F., Lavrik O.I. «Hydrazinothiazole derivatives of usnic acid exhibiting an inhibitory effect on the human tyrosyl DNA phosphodiesterase 1 enzyme».
• Patent - No. 2689335, Priority date from 02/16/2018, Salomatina O.V., Zakharenko A.L., Popadyuk I.I., Dyrkheeva N.S., Johannes R., Volcho K.P., Lavrik O .I., Salakhutdinov N.F. «Means for inhibiting of tyrosyl DNA phosphodiesterase 1 based on bile acids».
• Patent - No. 2 697 409 Priority date 30.04.2019. Published 14.08.2019, Oleshko O.S., Kovaleva K. S., Yarovaya O. I. Mamontova E. M., Zakharenko A. L., Zakharova O. D., Cheresiz S. V., Pokrovsky A. G., Lavrik O. I., Salakhutdinov N. F. “1-Adamantyl-3-(((1R,4aS,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl)methyl)urea, which has an inhibitory effect on the human tyrosyl-DNA-phosphodiesterase 1 enzyme and increases the activity of temozolomide against glioblastoma cells”.
• Patent - US 10,399,965,B2 PCT Jul.24, 2017. Published 03.09.2019, Luzina O.A., Zakharenko A.L., Sokolov D.N., Salakhutdinov N.F., Lavrik O.I., Khazanov V.A. “2-Acetyl-6-(2-(2-(4-bromobromobenzylidene)hydrazinyl)thiazole-4-yl)-3,7,9-trihydroxy-8,9B-dimethyl-dibenzo[,B,D]furan-1(9BH)-one exhibiting an inhibitory effect on human tyrosyl-DNA-phosphodiesterase 1 enzyme”.
• Patent - No. 2 724 878. Priority date 08.08.2019. Published on 26.06.2020. Khomenko T.M., Zakharenko A.L. Chepanova A.A., ilina E.S., Zakharova O.D., Kaledin V.I., Nikolin V.P., Popova N.A., Volcho K.P., Lavrik O.I., Salakhutdinov N.F. “A means for inhibiting the human tyrosyl-DNA-phosphodiesterase 1 enzyme based on phenylcoumarins, which sensitizes tumors to the action of antitumor agents”.

Laboratory is equipped by sets that are necessary to perform protein expression and purification, affinity labeling and other biochemical experiments. MALDI-MS analyses of DNA-protein complexes are performed with the equipment for general use of the Core Facility of Mass Spectrometric Analysis of ICBFM SB RAS.