Laboratory of Structural Biology
PROFILE
We combine structural biology (x-ray crystallography and electron microscopy), protein biochemistry as well as thermodynamic and kinetic approaches to understand at the molecular level the function of large macromolecular machines involved in DNA replication and repair processes.
RESEARCH TEAM
Laboratory of Structural Biology
Intercollegiate Faculty of Biotechnology UG&MUG
Abrahama 58 Street, 80-307 Gdańsk, Poland
Office: Ewa Kogut - tel.: +48 58 523 64 27 [e-mail]
STAFF LIST
Head: Assoc. Prof. Michał R. Szymański
Email: michal.szymanski@ug.edu.pl
michal.szymanski@biotech.ug.edu.pl
tel.: +48 58 523 6366
https://www.researchgate.net/profile/Michal_Szymanski2
Website: www.mrslab.ug.edu.pl
List of Employees and PhD students:
PhD Anna Karłowicz [e-mail]
telefon: +48 58 523 64 20
PhD eng. Karolina Kwiatkowska-Semrau [e-mail]
telefon: +48 58 523 64 20
PhD eng. Andrzej Dubiel [e-mail]
telefon: +48 58 523 64 20
PhD Grzegorz Grabe [e-mail]
telefon: +48 58 523 6434
PhD Ewa Dzik [e-mail]
telefon: +48 58 523 64 20
PhD Beata Walter
tel: +48 58 523 64 20 [email]
MSc Piotr Purzycki [email]
tel: +48 58 523 64 20
MSc Adela Bledea [email]
tel: +48 58 523 64 20
MSc Michał Majewski [email]
tel: +48 58 523 64 20
MSc Marta Wyszkowska [email]
tel: +48 58 523 64 20
MSc Karolina Zdrojewska [email]
tel: +48 58 523 64 20
Currently open positions:
soon
SCIENTIFIC AND RESEARCH PROJECTS
Tytuł projektu | Kierownik projektu | Źródło finansowania | Kwota | Lata realizacji |
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The structural organization of human mitochondrial replisome | Szymański Michał R. | SONATA BIS (NCN) | 4 791 600 zł | 2023 - 2028 |
Dynamics and evolution of specificity of TA complexes | Grabe Grzegorz | POLONEZ BIS (NCN) | 1 130 821 zł | 2023 - 2025 |
Biodiversity of bacteriophages: unusual DNA polymerases as exampels of surprising molecular diversity | Węgrzyn Alicja | OPUS (NCN) | 2 755 980 zł | 2023 - 2027 |
Structure and function of MPV17, a channel critical for mitochondrial DNA metabolism | Szymański Michał R. |
EMBO Small Pilot Grant |
10 000 EUR | 2022 |
Dissecting the mechanism of DNA repair in human mitochondria (MitoRepairosome) | Szymański Michał R. | ERC Starting Grant | 1 500 000 EURO |
2020 - 2025 |
Structural basis for DNA repair in human mitochondria | Szymański Michał R. | EMBO Installation Grant | 250 000 EURO |
2019 - 2024 |
Targeting mitochondrial DNA repair for novel anti-cancer therapies | Szymański Michał R. | First TEAM 3 | 3 680 750 zł |
2018 - 2023 |
Unraveling the molecular basis of DNA damage recognition and processing in human mitochondria | Szymański Michał R. | POLONEZ 2 | 944 874 zł |
2017 - 2019 |
PUBLICATIONS
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Szymański Michał R., Karłowicz Anna, Herrmann Geoffrey K., Cen Yana, Yin Y. Whitney. Human EXOG Possesses Strong AP Hydrolysis Activity: Implication on Mitochondrial DNA Base Excision Repair. Journal of the American Chemical Society 2022, 144(51) 23543–23550 (doi: 10.1021/jacs.2c10558)
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Karłowicz Anna, Dubiel Andrzej B., Czerwińska Jolanta, Bledea Adela, Purzycki Piotr, Grzelewska Marta, McAuley Ryan J, Szczęsny Roman J, Brzuska Gabriela, Król Ewelina, Szczęsny Bartosz, Szymański Michał R... In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing. Nucleic Acid Research 2022, 50(14): 7991-8007 (doi: 10.1093/nar/gkac581)
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Ahlqvist Josefin, Linares-Pastén Javier, Håkansson Maria, Jasilionis Andrius, Kwiatkowska-Semrau Karolina, Friðjónsson Ólafur H., Kaczorowska Anna, Dabrowski Slawomir, Aevarsson Arnthór, Hreggviðsson Guðmundur Ó., Al-Karadaghi Salam, Kaczorowski Tadeusz, Nordberg Karlsson Eva. Crystal structure and initial characterization of a novel archaeal-like Holliday junction-resolving enzyme from Thermus thermophilus phage Tth15-6. Acta Crystallographica Section D- Structural Biology 2022, 78: 212-227 (doi: 10.1107/s2059798321012298)
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Aevarsson Arnthór, Kaczorowska Anna-Karina, Adalsteinsson Björn Thor, Ahlqvist Josefin, Al-Karadaghi Salam, Altenbuchner Joseph, Arsin Hasan, Átlasson Úlfur Áugúst, Brandt David, Cichowicz-Cieślak Magdalena, Cornish Katy A S, Courtin Jérémy, Dabrowski Slawomir, Dahle Håkon, Djeffane Samia, Dorawa Sebastian, Dusaucy Julia, Enault Francois, Fedøy Anita-Elin, Freitag-Pohl Stefanie, Fridjonsson Olafur H, Galiez Clovis, Glomsaker Eirin, Guérin Mickael, Gundesø Sigurd E, Gudmundsdóttir Elisabet E, Gudmundsson Hördur, Håkansson Maria, Henke Christian, Helleux Alexandra, Henriksen Jørn Remi, Hjörleifdóttir Sigrídur, Hreggvidsson Gudmundur O, Jasilionis Andrius, Jochheim Annika, Jónsdóttir Ilmur, Jónsdóttir Lilja Björk, Jurczak-Kurek Agata, Kaczorowski Tadeusz, Kalinowski Jörn, Kozlowski Lukasz P, Krupovic Mart, Kwiatkowska-Semrau Karolina, Lanes Olav, Lange Joanna, Lebrat Julien, Linares-Pastén Javier, Liu Ying, Lorentsen Steffen A, Lutterman Tobias, Mas Thibaud, Merré William, Mirdita Milot, Morzywołek Agnieszka, Ndela Eric Olo, Karlsson Eva Nordberg, Olgudóttir Edda, Pedersen Cathrine, Perler Francine, Pétursdóttir Sólveig K, Plotka Magdalena, Pohl Ehmke, Prangishvili David, Ray Jessica L, Reynisson Birkir, Róbertsdóttir Tara, Sandaa Ruth-Anne, Sczyrba Alexander, Skírnisdóttir Sigurlaug, Söding Johannes, Solstad Terese, Steen Ida H, Stefánsson Sigmar Karl, Steinegger Martin, Overå Katrine Stange, Striberny Bernd, Svensson Anders, Szadkowska Monika, Tarrant Emma J, Terzian Paul, Tourigny Mathilde, Bergh Tom van den, Vanhalst Justine, Vincent Jonathan, Vroling Bas, Walse Björn, Wang Lei, Watzlawick Hildegard, Welin Martin, Werbowy Olesia, Wons Ewa, Zhang Ruoshi. Going to extremes - a metagenomic journey into the dark matter of life. FEMS Microbiology Letters 2021, 368(12): fnab067 (doi: 10.1093/femsle/fnab067)
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Reyes-Aldrete Emilio, Dill Erik A., Bussetta Cecile, Szymański Michał R., Diemer Geoffrey, Maindola Priyank, White Mark A., Bujalowski Wlodzimierz M., Choi Kyung H., Morais Marc C. . Biochemical and Biophysical Characterization of the dsDNA packaging motor from the Lactococcus lactis bacteriophage asccphi28. Viruses 2021, 13(1): 15 (doi: 10.3390/v13010015)
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Werbowy Olesia, Stefańska-Kaźmierczak Aleksandra, Jurczak-Kurek Agata, Kwiatkowska-Semrau Karolina, Kaczorowska Anna-Karina, Płotka Magdalena , Fridjonsson Olafur H., Hreggvidsson Gudmundur O., Dąbrowski Sławomir, Kaczorowski Tadeusz. The Characteristics of New SSB Proteins from Metagenomic Libraries and Their Use in Biotech Applications. Proceedings 2020, 50(1): 135 (doi: 10.3390/proceedings2020050135)
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Dosekova Petra,Dubiel Andrzej, Karłowicz Anna, Ziętkiewicz Szymon, Rydzanicz Małgorzata, Habalova Viera, Pieńkowski Victor Murcia, Skirkova Miriam, Han Vladimir, Mosejova Alexandra, Gdovinova Zuzanna, Kaliszewska Magdalena, Tońska Katarzyna,Szymański Michał R., Skorvanek Matej, Płoski Rafał. Answer to Finsterer about "Multisystem presentation of a homozygous POLG2 variant". European Journal of Medical Genetics. 2020, 63(5):103900 (doi: 10.1016/j.ejmg.2020.103900)
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Jain Nimit, Blauch Lukas R., Szymański Michał R., Das Rhiju, Tang Sindy K.Y., Yin Y. Withney, Fire Andrew Z. Transcription polymerase–catalyzed emergence of novel RNA replicons. Science 2020, 368(6487): eaay0688, (doi: 10.1126/science.aay0688)
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Dosekova Petra, Dubiel Andrzej, Karłowicz Anna, Ziętkiewicz Szymon, Rydzanicz Małgorzata, Habalova Viera, Pieńkowski Victor Murcia, Skirkova Miriam, Han Vladimir, Mosejova Alexandra, Gdovinova Zuzanna, Kaliszewska Magdalena, Tońska Katarzyna, Szymański Michał R., Skorvanek Matej, Płoski Rafał. Whole exome sequencing identifies a homozygous POLG2 missense variantin an adult patient presenting with optic atrophy, movement disorders,premature ovarian failure and mitochondrial DNA depletion. European Journal of Medical Genetics 2020, (w druku) (10.1016/j.ejmg.2019.103821)
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Szymanski, M.R., Yu, A., Gmyrek, A.M., White, M.A., Molineux, I.J., Lee, J.C., Yin W.Y. A novel domain in human EXOG converts apoptotic endonuclease to DNA- repair exonuclease. Nature Communications. 2017 May 3;8:14959. Recommended by F1000.
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Li, M., Mislak, A.C., Foli, Y., Agbosu, E., Bose, V., Bhandari, S., Szymanski, M.R., Shumate, C.K., Yin, W., Anderson, K.S., Paintsil, E. DNA Polymerase-γ R953C Mutant Linked to ART-Associated Mitochondrial Toxicity. Antimicrobial Agents and Chemotherapy. 2016 Aug 22;60(9):5608-11.
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Sohl, C.D*., Szymanski, M.R*., Mislak, A.C., Shumate, K.C., Amiralaei, S., Schinazi, F.R., Anderson K.S., Yin W.Y. Probing the Structural and Molecular Basis of Nucleotide Selectivity by Human Mitochondrial DNA Polymerase γ. Proceedings of National Academy of Sciences of the United States of America. 2015 Jul 14;112(28):8596-601. *equal contribution
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Szymanski, M.R., Kuznetsov, V.B., Shumate, C., Meng, Q., Lee, Y-S., Patel, G., Patel, S.S., Yin W.Y. Structural basis for processivity and antiviral drug toxicity in human mitochondrial DNA replicase. EMBO J. 2015 Jul 14; 34(14):1959-70.
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Szymanski, M.R., Jezewska, M.J., Bujalowski, W. The Escherichia Coli Primosomal DnaT Protein Exists in Solution as a Monomer – Trimer Equilibrium System. Biochemistry. 2013 Mar 19;52(11):1845-57.
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Szymanski, M.R., Jezewska, M.J., Bujalowski, W. Energetics of the Escherichia Coli DnaT Protein Trimerization Reaction. Biochemistry. 2013 Mar 19;52(11):1858-73.
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Szymanski, M.R., Bujalowski, P.J., Jezewska, M.J., Gmyrek, A.M., and Bujalowski, W. The N-terminal domain of the Escherichia coli PriA helicase contains both the DNA- and nucleotide-binding sites. Energetics of domain-DNA interactions and allosteric effect of the nucleotide cofactors. Biochemistry. 2011 Nov 1;50(43):9167-83.
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Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Binding of Two PriAPriB Complexes to the Primosome Assembly Site Initiates Primosome Formation. Journal of Molecular Biology. 2011 Aug 5;411(1):123-42.
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Szymanski, M.R., Jezewska, M.J., Bujalowski, P.J., Bussetta, C., Ye, M., Choi K.H., Bujalowski, W. Full-Length Dengue Virus RNA Dependent RNA Polymerase – RNA/ DNA Complexes. Stoichiometries and Energetics of Intrinsic Affinities, Cooperativities, Base and Conformational Specificities. Journal of Biological Chemistry. 2011 Sep 23;286(38):33095-108.
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Jezewska, M.J., Szymanski, M.R., and Bujalowski, W. Kinetic mechanism of the ssDNA recognition by the polymerase X from African Swine Fever Virus. Dynamics and energetics of intermediate formations. Biophysical Chemistry. 2011 Sep;158(1):9-20.
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Jezewska, M.J., Szymanski, M.R., and Bujalowski, W. Interactions of the DNA polymerase X from African Swine Fever Virus with the ssDNA. Properties of the total DNA-binding site and the strong DNA-binding subsite. Biophysical Chemistry. 2011 Sep;158(1):26-37.
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Jezewska, M.J., Szymanski, M.R., and Bujalowski, W. The primary DNAbinding subsite of the rat pol beta. Energetics of interactions of the 8-kDa domain of the enzyme with the ssDNA. Biophysical Chemistry. 2011 Jul;156(2-3):115-27.
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Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. The Escherichia coli PriA helicase-double-stranded DNA complex: location of the strong DNA-binding subsite on the helicase domain of the protein and the affinity control by the two nucleotide-binding sites of the enzyme. Journal of Molecular Biology. 2010 Sep 17;402(2):344-62.
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Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Interactions of the Escherichia coli primosomal PriB protein with the single-stranded DNA. Stoichiometries, intrinsic affinities, cooperativities, and base specificities. Journal of Molecular Biology. 2010 Apr 23;398(1):8-25.
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Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. The Escherichia coli PriA helicase specifically recognizes gapped DNA substrates: effect of the two nucleotide-binding sites of the enzyme on the recognition process. Journal of Biological Chemistry. 2010 Mar 26;285(13):9683-96.
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Andreeva, I.E., Roychowdhury, A., Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Mechanisms of interactions of the nucleotide cofactor with the RepA protein of plasmid RSF1010. Binding dynamics studied using the fluorescence stopped-flow method. Biochemistry. 2009 Nov 10;48(44):10620-36.
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Szymanski, M.R., Fiebach, A.R., Tratschin, J.D., Gut, M., Ramanujam, V.M., Gottipati, K., Patel, P., Ye, M., Ruggli, N., and Choi, K.H. Zinc binding in pestivirus N(pro) is required for interferon regulatory factor 3 interaction and degradation. Journal of Molecular Biology. 2009 Aug 14;391(2):438-49.
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Roychowdhury, A., Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Interactions of the Escherichia coli DnaB-DnaC protein complex with nucleotide cofactors. 1. Allosteric conformational transitions of the complex. Biochemistry. 2009 Jul 28;48(29):6712-29.
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Roychowdhury, A., Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Mechanism of NTP hydrolysis by the Escherichia coli primary replicative helicase DnaB protein. 2. Nucleotide and nucleic acid specificities. Biochemistry. 2009 Jul 28;48(29):6730-46.
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Roychowdhury, A., Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Escherichia coli DnaB helicase-DnaC protein complex: allosteric effects of the nucleotides on the nucleic acid binding and the kinetic mechanism of NTP hydrolysis. 3. Biochemistry. 2009 Jul 28;48(29):6747-63.
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Andreeva, I.E., Szymanski, M.R., Jezewska, M.J., Galletto, R., and Bujalowski, W. Dynamics of the ssDNA recognition by the RepA hexameric helicase of plasmid RSF1010: analyses using fluorescence stopped-flow intensity and anisotropy methods. Journal of Molecular Biology. 2009 May 15;388(4):751-75.
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Duret, G., Szymanski, M., Choi, K.J., Yeo, H.J., and Delcour, A.H. The TpsB translocator HMW1B of haemophilus influenzae forms a large conductance channel. Journal of Biological Chemistry. 2008 Jun 6;283(23):15771-8.
INTERNATIONAL SCIENTIFIC COOPERATION
Dr. Bartosz Szczesny, University of Texas Medical Branch at Galveston, Galveston, TX, USA
Dr. Whitney Yin, University of Texas Medical Branch at Galveston, Galveston, TX, USA
Dr. Wlodek M. Bujalowski (UTMB), University of Texas Medical Branch at Galveston, Galveston, TX, USA