Research

Overview

Silvia Onesti

Curriculum vitae: Degree in Chemistry, University of Pavia. PhD in Biophysics with David Blow and Peter Brick, Imperial College London.  Postdoctoral Fellow, Biophysics Section, Imperial College London.  Maître de conférences, Ecole Polytechnique, Palaiseau, Paris.  Lecturer, Physics Department, Imperial College London.  Senior Lecturer, Department of Life Sciences, Imperial College London. Current position: Head of Structural Biology, Elettra - Sincrotrone Trieste. Teaching Structural Biology at SISSA.

Contact details: Address: Sincrotrone Trieste S.C.p.A. SS 14 - km 163,5 AREA Science Park 34149 Basovizza, Trieste, Italy Tel: +39-040-3758451 Mobile: +39-366-6878001 Email: silvia.onesti@elettra.eu ORCID: http://orcid.org/0000-0002-0612-7948 Personal webpage:  http://www.elettra.trieste.it/People/SilviaOnesti.HomePage

Our research is mainly centered on the structural characterisation of proteins and protein complexes involved in the process of DNA replication and DNA repair in eukaryotic cells. Wherever possible, we will also use the simpler and more stable counterparts present in archaeal organisms.
Eukaryotic DNA replication is a highly coordinated and tightly regulated process. Due to the large genome size, eukaryotic cells initiates DNA replication at multiple origins and complex networks of proteins, under strict cell-cycle control, are required to ensure that each origin is used only once and no segment of DNA is left un-replicated or undergoes multiple rounds of replication. At the same time the DNA needs to be constantly protected and repaired from the damage caused by physical and chemical agents. Although recent genetic and genomic approaches have identified many of the key players in these processes, the detailed analysis of their architecture and the biochemical role of each component is still in progress.

Although the purified MCM2-7 is not very active, a stable complex comprising Cdc45, MCM2-7 and GINS can be co-purified and has a significant ATP-dependent helicase activity (Onesti&MacNeill, 2013; Medagli et al., 2016).  Cdc45 is an essential protein conserved in all eukaryotes and is involved in both the initiation of DNA replication and the progression of the replication fork. We detected a weak but significant relationship among eukaryotic Cdc45 proteins and a large family of phosphoesterases that has been described as DHH family, including inorganic pyrophosphatases and RecJ ssDNA exonucleases (Krastanova et al., 2012). Like the RecJ exonucleases, the recombinant human Cdc45 protein is able to bind single-stranded, but not double-stranded DNA. Small angle X-ray scattering data are consistent with a model compatible with the crystallographic structure of the RecJ/DHH family members.

RecQ helicases (A. Mojumdar, I. Bagnano, F. Marino, J. Morimoto, M. De March, S. Kenig)

PCNA and associate factor PAF15 (Scientist in charge: A. De Biasio; M. De March)

Proliferating Cell Nuclear Antigen (PCNA), the eukaryotic DNA sliding clamp, directs DNA replication and repair by harboring replicative polymerases and other factors. We have recently unveiled the structural basis of the mechanism of sliding of human PCNA on DNA ‒ a helical motion based on short-lived polar interactions ‒ which sheds new light onto previous observations on the function of the PCNA‒polymerase δ holoenzyme (De March et al., 2017). PCNA also interacts with the PCNA-associated factor PAF15, an oncogenic intrinsically disordered protein involved in the regulation of DNA replication and DNA damage bypass (De Biasio et al., 2014; De biasio et al., 2015). We are currently studying the effects of PAF15 on PCNA sliding on DNA, by combining structural studies, molecular dynamics simulations (in collaboration with Ramon Creuhet at the Institute of Advanced Chemistry of Catalonia), and single-molecule methods (in collaboration with Jong-Bong Lee at Postech University). Our long-term goal is to elucidate the mechanistic role of PAF15 in the processes of DNA replication and Translesion Synthesis (TLS), and to gain insight into how PAF15 dysregulation may contribute to cancer development.
http://www.elettra.trieste.it/science/top-stories/structural-basis-of-human-pcna-sliding-on-dna.html

Matteo "Jim Watson" De March uses his earphones to illustrate a novel mechanism of sliding of PCNA on DNA based on MD data.

Cyclic nucleotide-gated (CNG) channels play important roles in transmitting information about vision and smell from sensory cells to the brain, and share a high degree of similarity with K+ channels. Whereas K+ channels discriminate with high accuracy Na+ from K+, CNG channels do not discriminate among different cations. In collaboration with the laboratories of V. Torre and A. Laio (SISSA), we carried out a multidisciplinary study to better understand the specific behaviour of these important membrane proteins. We determined the crystal structure of this protein in complex with a variety of cations  of varying sizes (Li+, Na+, Rb+, Cs+, methylammonium, dimethylammonium). By combining electrophysiology, molecular dynamics simulations and X-ray crystallography we found that the pore region exhibits a dynamic structure and the pore diameter critically depends on the ion within and that a few key residues exhibit large conformational changes. We conclude that the pore of CNG channels is highly flexible and that this flexibility is at the basis of their poor ionic selectivity (Napolitano et al., 2015).

Selected Publications

(*Corresponding author)

• Bottega R., Ravera S., Napolitano L.M.R., Chiappetta V., Zini N., Crescenzi B., Arniani S., Faleschini M., Cortone G., Faletra F., Medagli B., Sirchia F., Moretti M., de Lange J., Cappelli E., Mecucci C., Onesti S., Pisani F.M., Savoia A.* (2021). Mitochondrial defect in Warsaw syndrome cells genomic integrity and mitochondrial metabolism defects in Warsaw syndrome cells: A comparison with Fanconi anemia. J Cell Physiol. Online ahead of print.
• De March M., Onesti S.*, De Biasio A.* (2020) Reply to: "Does PCNA diffusion on DNA follow a rotation-coupled translation mechanism?" Nat. Commun. 11, 4999.
• Ullah R., Shehzad A., Ali Shah M., De March M., Ismat F., Iqbal M., Onesti S., Rahman M., McPherson M.J.* (2020). C-Terminal Domain of the Human Zinc Transporter hZnT8 Is Structurally Indistinguishable From Its Disease Risk Variant (R325W). Int J Mol Sci, 21, 926.
• Lazzari E., El-Halawany M., De March M., Valentino F., Cantatore F., Migliore C., Onesti S., Meroni G.* (2019). Analysis of the Zn-binding domains of TRIM32, the E3 ubiquitin ligase mutated in Limb Girdle Muscular Dystrophy 2H. Cells, 8, E254.
• Bottega R., Napolitano L.M.R., Carbone A., Cappelli E., Corsolini F., Onesti S., Savoia A., Gasparini P., Faletra F.* (2019). Two further patients with Warsaw breakage syndrome. Is a mild phenotype possible? Mol. Genet. Genom. Med. 7, e693.
• Gonzalez-Magaña A., Ibáñez de Opakua A., Romano-Moreno M., Murciano-Calles J., Merino N., Luque I., Rojas A.L., Onesti S., Blanco F.J., De Biasio A.* (2019). The p12 subunit of human polymerase δ uses an atypical PIP-box for molecular recognition of proliferating cell nuclear antigen (PCNA). J. Biol. Chem. 294, 3947-3956.
• Pisani F.M.*, Napolitano E., Napolitano L.M.R., Onesti S.* (2018). Molecular and Cellular Functions of the Warsaw Breakage Syndrome DNA Helicase DDX11. Genes, 9, 564. 
• De March M., Barrera-Vilarmau S., Crespan E., Mentegari E., Merino N., Gonzalez-Magaña A., Romano-Moreno M., Maga G., Crehuet R., Onesti S., Blanco F.J., De Biasio A.* (2018). p15^PAF binding to PCNA modulates the DNA sliding surface. Nucleic Acids Res. 46, 9816-9828.
• Napolitano L.M.R., Marchesi A., Rodriguez A., De March M., Onesti S., Laio A.*, Torre V..* (2018). The permeation mechanism of organic cations through a CNG mimic channel. PLoS Comput. Biol. 14, e1006295.
• Ali Shah M., Ullah R., De March M., Salahuddin Shaha M., Ismata F., Habib M., Iqbala M., Onesti S., Rahman M.* (2017). Overexpression and characterization of the 100K protein of Fowl adenovirus-4 as an antiviral target. Virus Research    238, 218-225.
• Deka J., Mojumdar A., Parisse P., Onesti S.* and Casalis L.* (2017). DNA-conjugated gold nanoparticles based colorimetric assay to assess helicase activity: a novel route to screen potential helicase inhibitors. Scientific Rep. 7, 44358.
• De March M., Merino N., Barrera-Vilarmau S., Crehuet R., Onesti S.*, Blanco F.S.* and De Biasio A.* (2017). Structural basis of human PCNA sliding on DNA. Nat. Commun. 7, 13935.
• Carroni M., De March M., Medagli B., Krastanova I.,Taylor I.A., Amenitsch H., Araki H., Pisani F.M., Patwardhan A. and Onesti S.* (2017). New insights into the GINS complex explain the controversy between existing structural models. Scientific Rep. 7, 40188.
• Mojumdar A., De March M., Marino F. and Onesti S*. (2017) The human RecQ4 helicase contains a functional RQC domain that is essential for activity. J. Biol. Chem. 292, 4176-4184
• Ormaza G., Medagli B., Rodríguez J.A., Ibáñez de Opakua A., Merino N., Villate M., Onesti S. and Blanco F.J.* (2016). The tumor suppressor ING4 binds double stranded DNA with micromolar affinity through its disordered central region. FEBS Letters. 591, 425-432.
• Marino F., Mojumdar A., Zucchelli C. Bhardwaj A., Buratti E., Vindigni A., Musco G. and Onesti S.* (2016). Structural and biochemical characterization of an RNA/DNA binding motif in the N-terminal domain of RecQ4 helicases. Scientific Rep. 6, 21501.
• Medagli B., Di Crescenzio P., De March M. and Onesti S.* (2016). Structure and activity of the Cdc45-Mcm2-7-GINS (CMG) complex, the replication helicase. (Chapter in "The initiation of DNA replication in eukaryotes", Ed. D. Kaplan, Springer).
• Napolitano L.M.R., Bisha I., De March M., Marchesi A., Arcangeletti M., Demitri N., Mazzolini M., Rodriguez A., Magistrato A., Onesti S.*, Laio A.* and Torre V.* (2015). A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels. Proc. Natl. Acad. Sci. USA. E3619-E3628. 
• Wiedemann C., Ohlenschläger O., Medagli B., Onesti S. and Görlach M. (2013). ¹H,  ¹⁵N and ¹³C chemical shift assignments for the winged helix domains of two archeal MCM C-termini. Biomol NMR Assign.  
• Marino F., Vindigni A. and Onesti S.* (2013) Bioinformatic analysis of RecQ4 helicases reveals the presence of a RQC domain and a Zn knuckle. Biophys Chem. 177-178, 34-39. 
• Onesti S. and MacNeill S.A.* (2013) Structure and evolutionary origins of the CMG complex. Chromosoma. 122, 47-53.
• Medagli B. and Onesti S.* (2013). Structure and mechanism of hexameric helicases. Adv. Exp. Med. Biol. 767, 75-95 (Chapter in "DNA helicases and DNA motor proteins", Ed. M. Spies, Springer).
• Krastanova I., Sannino V., Amenitsch H., Gileadi O., Pisani F.M. and Onesti S.* (2012). Structural and functional insights into the DNA replication factor Cdc45 reveal an evolutionary relationship to the DHH family of phosphoesterases. J. Biol. Chem. 287, 4121-4128.
• Costa A. and Onesti S.* (2009). Structural biology of MCM helicases. Crit. Rev. Biochem. Mol. Biol. 44, 326-342.
• Costa A., Van Dujinen G., Medagli B., Chong J., Sakakibara N., Kelman Z., Nair S.K., Patwardhan A. and Onesti S.* (2008). Cryo-electron microscopy reveals a novel DNA binding site on the MCM helicase. EMBO J. 27, 2250-2258.
• Costa A., Pape T., van Heel M., Brick P., Patwardhan A. and Onesti S.* (2006). Structural basis of the Methanobacter thermautotrophicus MCM helicase activity. Nucleic Acid Res. 34, 5829-5838.
• Paraskevopoulou C., Fairhurst S.A., Lowe D.J., Brick P. and Onesti S.* (2006). The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine. Mol. Microbiol. 59, 795-806.
• Meka H., Werner F., Cordell, S., Onesti S. and Brick P.* (2005). Crystal structure and RNA binding of the Rpb4/Rpb7 subunits of human RNA polymerase II. Nucleic Acid Res. 33, 6435-6444.
• Pape T., Meka H., Chen S., Vicentini G., van Heel M. and Onesti S.* (2003). Hexameric ring structure of the full-length archaeal MCM complex. EMBO Rep. 4, 1079-1083.
• Meka H., Daoust G., Bourke-Arnvig K., Werner F., Brick P. and Onesti S.* (2003). Structural and functional homology between the RNAPI subunits A14/A43 and the archaeal RNAP subunits E/F. Nucleic Acid Res. 31, 4391-4400.
• Todone F., Brick P., Werner, F., Weinzierl R.O.J and Onesti S.* (2001). Structure of an archaeal homologue of the eukaryotic RNA polymerase II RPB4/RPB7 complex. Mol. Cell, 8, 1137-1143.
• Todone F., Weinzierl R.O.J, Brick P. and Onesti S.* (2000). Crystal structure of RPB5, a universal eukaryotic RNA polymerase subunit and transcription factor interaction target. Proc. Natl. Acad. Sci. USA, 97, 6306-6310.

Paola Storici

Curriculum vitae: Degree in Medicinal Chemistry, University of Trieste. PhD in Biochemistry, University of Trieste. Postdoctoral Fellow, Structural Biology, Biozentrum - Basel. Senior Scientist, R&D Oncology, Pharmacia - Milano. Head of Biochemistry, R&D Nerviano Medical Sciences - Milano. Current position: Senior Research Scientist, Elettra - Sincrotrone Trieste. Head of the Protein Production Facility

Contact details: Address: Elettra - Sincrotrone Trieste S.C.p.A. SS 14 - km 163,5 AREA Science Park 34149 Basovizza, Trieste, Italy Tel: +39-040-3758854 Mobile: +39-331-1921484 Email: paola.storici@elettra.eu Personal webpage:  http://www.elettra.eu/PEOPLE/index.php?n=PaolaStorici.HomePage

The group has three main objectives:

• Run the protein production facility to support research activity of public or private users 

• Investigate biochemical and structural properties of protein targets for therapy of cancer and neurodegenerative diseases

• Investigate structural properties of SARS-CoV-2 protein targets for identification of repourposed and novel drugs

   

The Protein Production Facility A Protein Facility is acive since 2015 at the Elettra synchrotron of Trieste taking advantage of the infrastructures and of the expertise existing in the structural biology laboratory. The protein production platform is organized for expression in E.coli, insect cells and mammalian cell systems, and is well equipped to go from small-scale constructs screening to mid/large-scale preparations, with strong capacity and competence in protein purification techniques. On average we support about 30 different protein projects a year from internal and external groups of academic or industrial R&D partners. In particular the lab intent is to facilitate the process to obtain recombinant proteins suitable for analysis with synchrotron radiation techniques (x-ray diffraction, SAXS, FTIR). The active projects are distinguished between collaborative research projects, industrial services and tutoring activities.  The main scientific interest is on protein targets for drug discovery with focus on treatments for cancer and neurodegenerative diseases. Most of the targets belong to two big proteins families of druggable targets: the human kinases and the deubiquitinases. In addition, our pipeline encompasses between different types of protein such as membrane proteins, proteases as well as nanobodies. The Facility is an active member of the P4EU Network (Protein Production and Purification Partnership in Europe; www.p4eu.org) and takes part in benchmarking activities to keep up with the state of the art of the protein production technology and to offer a validated process to partners.

Tecan Freedom EVO 150

Selected Publications

• Minnelli, C.; Laudadio, E.; Sorci, L.; Sabbatini, G.; Galeazzi, R.; Amici, A.; Semrau, M.S.; Storici, P.; Rinaldi, S.; Stipa, P.; Marcaccio, M.; Mobbili G. (2022) Identification of a novel nitroflavone-based scaffold for designing mutant-selective EGFR tyrosine kinase inhibitors targeting T790M and C797S resistance in advanced NSCLC. Bioorganic Chemistry, 106219. https://doi.org/10.1016/j.bioorg.2022.106219
• Semrau, M. S.; Giachin, G.; Covaceuszach, S.; Cassetta, A.; Demitri, N.; Storici, P.*; Lolli, G.* (2022) Molecular Architecture of the Glycogen- Committed PP1/PTG Holoenzyme. Nat Commun, 13 (1), 6199. https://doi.org/10.1038/s41467-022-33693-z.

• Pelliccia, S.; Cerchia, C.; Esposito, F.; Cannalire, R.; Corona, A.; Costanzi, E.; Kuzikov, M.; Gribbon, P.; Zaliani, A.; Brindisi, M.; Storici, P.; Tramontano, E.; Summa, V.  (2022) Easy Access to α-Ketoamides as SARS-CoV-2 and MERS Mpro Inhibitors via the PADAM Oxidation Route. European Journal of Medicinal Chemistry, 114853. https://doi.org/10.1016/j.ejmech.2022.114853.

• Balboni, B.; Tripathi, S. K.; Veronesi, M.; Russo, D.; Penna, I.; Giabbai, B.; Bandiera, T.; Storici, P.; Girotto, S.; Cavalli, A. (2022) Identification of Novel GSK-3β Hits Using Competitive Biophysical Assays. Int. J. Mol. Sci., 18. https://doi.org/10.3390/ijms23073856.

• Demuro, S.; Sauvey, C.; Tripathi, S. K.; Di Martino, R. M. C.; Shi, D.; Ortega, J. A.; Russo, D.; Balboni, B.; Giabbai, B.; Storici, P.; Girotto, S.; Abagyan, R.; Cavalli, A. (2022) ARN25068, a Versatile Starting Point towards Triple GSK-3β/FYN/DYRK1A Inhibitors to Tackle Tau-Related Neurological Disorders. European Journal of Medicinal Chemistry, 229, 114054. https://doi.org/10.1016/j.ejmech.2021.114054.

• Costanzi, E.; Kuzikov, M., Esposito, F., Albani, S., Demitri, N., Giabbai, B., Camasta, M., Tramontano, E., Rossetti, G., Zaliani, A., Storici, P. (2021). Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L. International Journal of Molecular Sciences, 22 (21), 11779. https://doi.org/10.3390/ijms222111779.

• Brullo C., Rapetti F., Abbate S., Prosdocimi T., Torretta A., Semrau M.S., Massa M., Alfei S., Storici P., Parisini E., Bruno O. (2021). Design, synthesis, biological evaluation and structural characterization of novel GEBR library PDE4D inhibitors. European Journal of Medicinal Chemistry, 223, 113638. https://doi.org/10.1016/j.ejmech.2021.113638

• Gossen J., Albani S., Hanke A., Joseph B. P., Bergh C., Kuzikov M., Costanzi E., Manelfi C., Storici P., Gribbon P., Beccari A. R., Talarico C., Spyrakis F., Lindahl E., Zaliani A., Carloni P., Wade R. C., Musiani F., Kokh D. B. Rossetti G. (2021). A Blueprint for High Affinity SARS-CoV-2 Mpro Inhibitors from Activity-Based Compound Library Screening Guided by Analysis of Protein Dynamics. ACS Pharmacology & Translational Science, 4(3), 1079–1095. https://doi.org/10.1021/acsptsci.0c00215

• Kuzikov M., Costanzi E., Reinshagen J., Esposito F., Vangeel L., Wolf M., Ellinger B., Claussen C., Geisslinger G., Corona A., Iaconis D., Talarico C., Manelfi C., Cannalire R., Rossetti G., Gossen J., Albani S., Musiani F., Herzog K., Ye Y., Giabbai B., Demitri N., Jochmans D., Jonghe S. D., Rymenants J., Summa V., Tramontano E., Beccari A. R., Leyssen P., Storici P., Neyts J., Gribbon P., Zaliani A. (2021). Identification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen. ACS Pharmacology & Translational Science, 4 (3), 1096–1110. https://doi.org/10.1021/acsptsci.0c00216

• Zucchiatti P., Birarda G., Cerea A., Semrau M.S., Hubarevich A.,Storici P., De Angelis F., Toma A., Vaccari L. (2021). Binding of tyrosine kinase inhibitor to epidermal growth factor receptor: Surface-enhanced infrared absorption microscopy reveals subtle protein secondary structure variations. Nanoscale, 13(16), 7667–7677. https://doi.org/10.1039/d0nr09200b

• Annunziato G., Spadini C., Franko N., Storici P., Demitri N., Pieroni M., Flisi S., Rosati L., Iannarelli M., Marchetti M., Magalhaes J., Bettati S., Mozzarelli A., Cabassi C. S., Campanini B., Costantino G. (2021). Investigational Studies on a Hit Compound Cyclopropane–Carboxylic Acid Derivative Targeting O-Acetylserine Sulfhydrylase as a Colistin Adjuvant. ACS Infectious Diseases, 7(2), 281–292. https://doi.org/10.1021/acsinfecdis.0c00378

• Battista T., Pascarella G., Staid D. S., Colotti G., Rosati J., Fiorillo A., Casamassa A., Vescovi A. L., Giabbai B., Semrau M.S., Fanelli S., Storici P., Squitieri F., Morea V., Ilari A. (2021). Known Drugs Identified by Structure-Based Virtual Screening Are Able to Bind Sigma-1 Receptor and Increase Growth of Huntington Disease Patient-Derived Cells. International Journal of Molecular Sciences, 22(3), 1293. https://doi.org/10.3390/ijms22031293

• Peleg Y., Vincentelli R., Collins B. M., Chen K.-E., Livingstone E. K., Weeratunga S., Leneva N., Guo Q., Remans K., Perez K., Bjerga G. E. K., Larsen Ø., Vaněk O., Skořepa O., Jacquemin S., Poterszman A., Kjær S., Christodoulou E., Albeck S., Dym, O., Ainbinder E., Unger T., Schuetz, A., Matthes, S., Bader, M., de Marco, A., Storici P., Semrau M.S., Stolt-Bergner P., Aigner C., Suppmann S., Goldenzweig A., Fleishman, S. J. (2021). Community-wide experimental evaluation of the pross stability-design method. Journal of Molecular Biology, 433(13), 166964. https://doi.org/10.1016/j.jmb.2021.166964

• Ubbiali D., Orlando M., Kovačič M., Iacobucci C., Semrau M.S., Bajc G., Fortuna S., Ilc G., Medagli B., Oloketuyi S., Storici P., Sinz A., Grandori R., de Marco A. (2021). An anti-HER2 nanobody binds to its antigen HER2 via two independent paratopes. International Journal of Biological Macromolecules, 182, 502–511. https://doi.org/10.1016/j.ijbiomac.2021.04.032

• Pachetti M., Marini B., Benedetti F., Giudici F., Mauro E., Storici P., Masciovecchio C., Angeletti S., Ciccozzi M., Gallo R. C., Zella D., & Ippodrino R. (2020). Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant.Journal of Translational Medicine,18(1), 179. https://doi.org/10.1186/s12967-020-02344-6

• Cavalloro V., Russo K., Vasile F, Pignataro L., Torretta A., Donini S., Semrau M.S., Storici P., Rossi D., Rapetti F., Brullo C., Parisini E., Bruno O., Collina S. (2020). Insight into GEBR-32a: Chiral Resolution, Absolute Configuration and Enantiopreference in PDE4D Inhibition. Molecules, 25(4), 935. https://doi.org/10.3390/molecules25040935

• Veggiani G., Giabbai B., Semrau M.S., Medagli B.,Riccio V., Bajc G.,Storici P., de Marco A. (2020). Comparative analysis of fusion tags used to functionalize recombinant antibodies. Protein Expression and Purification,166, 105505. https://doi.org/10.1016/j.pep.2019.105505

• Soler M.A., Medagli B., Semrau M.S., Storici P., Bajc G, de Marco A, Laio A, Fortuna S.* (2019). A consensus protocol for the in silico optimisation of antibody fragments. Chem Commun 19,14043-14046. doi: 10.1039/c9cc06182g.

• Rosa B., Marchetti M., Paredi G., Amenitsch H., Franko N., Benoni R., Giabbai B., De Marino M.G., Mozzarelli A., Ronda L., Storici P.*, Campanini B.*, Bettati S. (2019). Combination  of SAXS and Protein Painting Discloses the Three-Dimensional Organization of the Bacterial Cysteine Synthase Complex, a Potential Target for Enhancers of Antibiotic Action. Int J Mol Sci. 20. pii: E5219. doi:10.3390/ijms20205219. 

• Gobbo D., Piretti V., Di Martino R.M.C., Tripathi S.K., Giabbai B., Storici P., Demitri N., Girotto S., Decherchi S., Cavalli A. (2019). Investigating Drug-Target Residence Time in Kinases through Enhanced Sampling Simulations. J Chem Theory Comput. 15, 4646-4659. doi: 10.1021/acs.jctc.9b00104. Epub 2019.

• Redenti S., Marcovich I., De Vita T., Pérez C., De Zorzi R., Demitri N., Perez D.I., Bottegoni G., Bisignano P., Bissaro M., Moro S., Martinez A.,Storici P., Spalluto G., Cavalli A., Federico S. (2019). A Triazolotriazine-Based Dual GSK-3β/CK-1δ Ligand as a Potential Neuroprotective Agent Presenting Two Different Mechanisms of Enzymatic Inhibition. ChemMedChem. 14, 310-314. doi: 10.1002/cmdc.201800778.

• Carlino L., Christodoulou M.S., Restelli V., Caporuscio F., Foschi F., Semrau M.S., Costanzi E., Tinivella A., Pinzi L., Lo Presti .L, Battistutta R., Storici P., Broggini M., Passarella D., Rastelli G.* (2018). Structure-Activity Relationships of
  Hexahydrocyclopenta[c]quinoline Derivatives as Allosteric Inhibitors of CDK2 and EGFR. ChemMedChem. 13, 2627-2634. doi: 10.1002/cmdc.201800687.

• Raboni S., Revtovich S., Demitri N., Giabbai B., Storici P., Cocconcelli C., Faggiano S., Rosini E., Pollegioni L., Galati S., Buschini A., Morozova E., Kulikova V., Nikulin A., Gabellieri E., Cioni P., Demidkina T., Mozzarelli A.* (2018). Engineering methionine γ-lyase from Citrobacter freundii for anticancer activity. Biochim Biophys Acta Proteins Proteom. 1866, 1260-1270. doi:10.1016/j.bbapap.2018.09.011. 

• Caporuscio F, Tinivella A, Restelli V, Semrau MS, Pinzi L, Storici P, Broggini M, Rastelli G. (2018). Identification of small-molecule EGFR allosteric inhibitors by high-throughput docking. Future Med Chem. 10(13):1545-1553. doi: 10.4155/fmc-2018-0063. Epub 2018 May 16.

• Prosdocimi T, Mollica L, Donini S, Semrau MS, Lucarelli AP, Aiolfi E, Cavalli A, Storici P, Alfei S, Brullo C, Bruno O, Parisini E.* (2018). Molecular Bases of PDE4D Inhibition by Memory-Enhancing GEBR Library Compounds. Biochem. Biochemistry. 57(19):2876-2888. doi: 10.1021/acs.biochem.8b00288. Epub 2018 May 1.

• Stolt-Bergner P, Benda C, Bergbrede T, Besir H, Celie PHN, Chang C, Drechsel D, Fischer A, Geerlof A, Giabbai B, van den Heuvel J, Huber G, Knecht W, Lehner A, Lemaitre R, Nordén K, Pardee G, Racke I, Remans K, Sander A, Scholz J, Stadnik M, Storici P, Weinbruch D, Zaror I, Lua LHL, Suppmann S.* (2018). Baculovirus-driven protein expression in insect cells: A benchmarking study.  J.Struct Biol. 203:71-80. doi: 10.1016/j.jsb.2018.03.004. Epub 2018 Mar 12.

• Campaner E., Rustighi A., Zannini A., Cristiani A., Piazza S., Ciani Y., Kalid O., Golan G., Baloglu E., Shacham S., Valsasina B., Cucchi U., Pippione A.C., Lolli M., Giabbai B., Storici P., Carloni P., Rossetti G., Bello E., D’Incalci M., Sommaggio R., Cappuzzello E., Rosato A., and Del Sal G. A new covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action; Nat Commun. 2017 Jun 9;8:15772. doi: 10.1038/ncomms15772.

• Basters A., Geurink P.P., Röcker A., Witting K.F., Tadayon R., Hess S., Semrau M.S. , Storici P., Ovaa H., Knobeloch K-P*, and Fritz G. (2017). Structural basis for the specificity of USP18 towards ISG15. Nature Structural & Molecular Biology, 24, 270-278.

• Kenig S, Bedolla DE, Birarda G, Faoro V, Mitri E, Vindigni A, Storici P, Vaccari L. (2015) Fourier transform infrared microspectroscopy reveals biochemical changes associated with glioma stem cell differentiation. Biophys Chem.; 207:90-96. doi: 10.1016/j.bpc.2015.09.005. 

• Ronda L, Bruno S, Bettati S, Storici P, Mozzarelli A. (2015)  From protein structure to function via single crystal optical spectroscopy. Front Mol Biosci.28;2:12. doi: 10.3389/fmolb.2015.00012. 

• Gianoncelli A, Vaccari L, Kourousias G, Cassese D, Bedolla DE, Kenig S, Storici P, Lazzarino M, Kiskinova M. (2015) Soft X-Ray Microscopy Radiation Damage On Fixed Cells Investigated With Synchrotron Radiation FTIR Microscopy. Sci Rep. 2015 May 14;5:10250. doi: 10.1038/srep10250.

• Cersosimo U., Sgorbissa A., Foti C., Drioli S., Angelica R., Tomasella A., Picco R., Semrau M., Storici  P., Benedetti F., Berti F., Brancolini C. (2015)  Synthesis, Characterization and Optimization for in Vivo Delivery of a Non-Selective Isopeptidase Inhibitor as New Anti-Neoplastic Agent.  J.Med.Chem. 26;58(4):1691-704. doi: 10.1021/jm501336h. Epub 2015 Feb 12.

• Bedolla D., Kenig S., Mitri E., Storici P., Vaccari L. (2014) Further insights into G1 and G0 phases of cell cycle revealed by FTIR microspectroscopy. Vib. Spec. 75: 127-135. DOI: 10.1016/j.vibspec.2014.08.007 

• Bindi S, Fancelli D, Alli C, Berta D, Bertrand JA, Cameron AD, Cappella P, Carpinelli P, Cervi G, Croci V, D'Anello M, Forte B, Giorgini ML, Marsiglio A, Moll J, Pesenti E, Pittalà V, Pulici M, Riccardi-Sirtori F, Roletto F, Soncini C,Storici P, Varasi M, Volpi D, Zugnoni P, Vianello P. (2010). Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable antitumor activity. Bioorg Med Chem. 18, 7113-7120.

• Beria I, Ballinari D, Bertrand JA, Borghi D, Bossi RT, Brasca MG, Cappella P, Caruso M, Ceccarelli W, Ciavolella A, Cristiani C, Croci V, De Ponti A, Fachin G, Ferguson RD, Lansen J, Moll JK, Pesenti E, Posteri H, Perego R, Rocchetti M, Storici P, Volpi D and Valsasina B. (2010). Identification of 4,5-Dihydro-1H-pyrazolo[4,3-h]quinazoline Derivatives as a New Class of Orally and Selective Polo-Like Kinase 1 Inhibitors. J Med Chem. 53, 3532-3551.

• Carpinelli P, Ceruti R, Giorgini ML, Cappella P, Gianellini L, Croci V, Degrassi A, Texido G, Rocchetti M, Vianello P, Rusconi L, Storici P, Zugnoni P, Arrigoni C, Soncini C, Alli C, Patton V, Marsiglio A, Ballinari D, Pesenti E, Fancelli D, Moll J. (2007) PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer. Mol. Cancer Ther. 6, 3158-3168.

• Fancelli D, Moll J, Varasi M, Bravo R, Artico R, Berta D, Bindi S, Cameron A, Candiani I, Cappella P, Carpinelli P, Croci W, Forte B, Giorgini ML, Klapwijk J, Marsiglio A, Pesenti E, Rocchetti M, Roletto F, Severino D, Soncini C,  Storici P, Tonani R, Zugnoni P, and Vianello P (2006) 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: Identification of a Potent Aurora Kinases Inhibitor with a Favorable Antitumor Kinase Inhibition Profile, J Med Chem 49, 7247-7251.

• Soncini C, Carpinelli P, Giannellini L, Fancelli D, Vianello P, Rusconi L, Storici P, Zugnoni P, Pesenti E, Croci V, Ceruti R, Giorgini ML, Cappella P, Ballinari D, Sola F, Varasi M & Bravo R (2006),  PHA680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin.Cancer Res. 12, 4080-4090.

• Baslé A, Rummel G, Storici P, Rosenbusch J.P .and Schirmer T (2006), X-ray crystal structure of osmoporin OmpC from E. coli at 2.0 Å. J.Mol.Biol. 362, 933-942

• Fancelli D, Berta D, Bindi S, Cameron A, Cappella P, Carpinelli P, Catana C, Forte B, Giordano P, Giorgini ML, Mantegani S, Marsiglio A, Meroni M, Moll J, Pittala V, Roletto F, Severino D, Soncini C, Storici P, Tonani R, Varasi M, Vulpetti A, Vianello P. (2005) Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 48, 3080-3084.

• Storici P, Qiu J, Schirmer T, Silverman RB. (2004) Mechanistic crystallography. Mechanism of inactivation of gamma-aminobutyric acid aminotransferase by (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid as elucidated by crystallography. Biochemistry 43, 14057-14063.

• Storici P., De Biase D., Bossa F., Bruno, S., Mozzarelli A., Peneff C., Silverman R.B. and Schirmer T. (2004) Structures of g-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin. J Biol Chem. 279, 363-373.
   

Alessandro Vindigni

Curriculum vitae: Degree in Chemistry, University of Padua. PhD in Biochemistry and Molecular Biophysics, University of Padua. 1995-1999 Postdoctoral Fellow, Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis. 1999-2002 Staff Scientist, Molecular Biology Group, ICGEB, Trieste. 2002-2012 Group Leader, Genome Stability Group, ICGEB, Trieste. Current positions: Associate Professor, Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine. Distinguished Scientist, Sincrotrone Trieste S.C.p.A., Trieste.

Contact details: Address: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1100 South Grand Blvd, St. Louis, MO 63104, USA Tel: +1-314-977-9217 Email: avindigni@slu.edu Webpage: http://biochemweb.slu.edu/people/faculty/vindigni.shtml

Agents that stall or damage DNA replication forks are widely used for chemotherapy, in the attempt to selectively target highly proliferating cancer cells. Our group studies the mechanisms that operate in eukaryotic cells to maintain replication fork integrity upon chemical treatment with cancer chemotherapeutics.
 
Replication fork reversal is rapidly emerging as a pivotal mechanism to explain how stalled or damaged replication forks are processed upon treatment with cancer chemotherapeutics. This mechanism invokes formation of four-way junction structures, reminiscent of Holliday junctions, to prevent the collision of the replication fork with the damage ahead of the fork. We are combining cellular, biochemical and structural approaches to define the exact molecular mechanisms used by eukaryotic ATP-dependent motor proteins to resolve these potentially recombinogenic four-way junction/reversed fork DNA structures that arise upon replication stress induction.
 
We are particularly interested into the function of RecQ helicases in this process because of their central roles in the resolution of several DNA replication and repair intermediates. Our studies highlighted a key role for the human RECQ1 helicase in promoting the efficient restart of replication forks that have reversed upon treatment with DNA topoisomerase I chemotherapeutic inhibitors. Based on these recent advances, the Elettra’s laboratory is actively involved in testing whether RecQ helicases represent a tractable target to improve current oncology regimens based on replication inhibitor treatment. 

Selected publications

• Quinet, A., Carvajal-Maldonado, D., Lemacon, D., Vindigni, A. (2017) DNA fiber analysis: mind the gap! Methods in Enzymol., [In press].
• Vindigni, A., Lopes, M. (2016) Combining electron microscopy with single molecule DNA fiber approaches to study DNA replication dynamics. Biophys. Chem., [Epub ahead of print].
• Kenig S., Faoro V., Bourkoula E., Podergajs N., Ius T., Vindigni M., Skrap M., Lah T., Cesselli D., Storici P., Vindigni A. (2016). Topoisomerase IIβ mediates the resistance of glioblastoma stem cells to replication stress-inducing drugs. Cancer Cell Int.16, 58.
• Pellarin, I., Arnoldo, L., Costantini, S., Pegoraro, S., Ros, G., Penzo, C., Triolo, G., Demarchi, F., Sgarra, R., Vindigni, A., Manfioletti G. (2016). The architectural chromatin factor high mobility group A1 enhances DNA ligase IV activity influencing DNA repair. PloS One 11, e0164258.
• Berti, M., Vindigni, A. (2016) Replication stress: getting back on track. Nat. Struct. Mol. Biol. 23, 103-109.
• Yamamoto, K., Wang, J., Sprinzen, L., Xu, J., Haddock, C.J., Li, C., Lee, B.J., Loredan, D.G., Jiang, W., Vindigni, A., Wang, D., Rabadan, R., Zha, S. (2016). Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors. Elife 5, e14709.
• Marino, F. Mojumdar, A., Zucchelli, C., Bhardwaj, A., Buratti, E., Vindigni, A., G., Onesti, S. (2016). Structural and biochemical characterization of an RNA/DNA binding motif in the N-terminal domain of RecQ4 helicases. Sci Rep. 6, 21501.
• Pike A.C., Gomathinayagam S., Swuec P., Berti M., Zhang Y., Schnecke C., Marino F., von Delft F., Renault L., Costa A., Gileadi O., Vindigni A. (2015). Human RECQ1 helicase-driven DNA unwinding, annealing, and branch migration: Insights from DNA complex structures. Proc. Natl. Acad. Sci. USA. 112, 4286-4291.
• Kenig, S., Bedolla, D.E., Birarda, G., Faoro, V., Mitri, E., Vindigni, A., Storici, P., Vaccari, L. (2015). Fourier transform infrared microspectroscopy reveals biochemical changes associated with glioma stem cell differentiation. Biophys Chem. 207, 90-96.
• Thangavel, S., Berti, M., Levikova, M., Pinto, C., Gomathinayagam, S., Vujanovic, M., Zellweger, R., Moore, H., Lee, E.H., Hendrickson, E.A., Cejka, P., Stewart, S., Lopes, M., Vindigni, A. (2015). DNA2 drives processing and restart of reversed replication forks in human cells. J. Cell Biol. 208, 563-579.
• Zellweger, R., Dalcher, D., Mutreja, K., Berti, M., Schmid, J., Herrador, R., Vindigni, A., Lopes, M. (2015). Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells. J. Cell Biol. 208, 545-562.
• Li, X.L., Lu, X., Parvathaneni, S., Bilke, S., Zhang, H., Thangavel, S., Vindigni, A., Hara, T., Zhu, Y., Meltzer, P.S., Lal, A., Sharma, S. (2014). Identification of RECQ1-regulated transcriptome uncovers a role of RECQ1 in regulation of cancer cell migration and invasion. Cell Cycle 13(15), 2431-2445.
• Vindigni A. and Gonzalo S. (2013) . The two faces of DNA repair: disease and therapy. Mol Med. 110, 314-319.
• Berti M., Chaudhuri A.R., Thangavel S., Gomathinayagam S., Kenig S., Vujanovic M., Odreman F., Glatter T., Graziano S., Mendoza-Maldonado R., Marino F., Lucic B., Biasin V., Gstaiger M., Aebersold R., Sidorova J.M., Monnat R.J. Jr, Lopes M. and Vindigni A. (2013). Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition. Nat Struct Mol Biol. 20, 347-354. 
• Marino F., Vindigni A. and Onesti S. (2013) Bioinformatic analysis of RecQ4 helicases reveals the presence of a RQC domain and a Zn knuckle. Biophys Chem. 177-178, 34-39. 
• Parisse, P., Vindigni, A., Scoles, G. and Casalis, L. (2012). In vitro enzyme comparative kinetics: unwinding of surface-bound DNA nanostructures by RecQ and RecQ1. J. Phys. Chem. Letters 3, 3532-3537.
• Mendoza-Maldonado, R., Faoro, V., Bajpai, S., Berti, M., Odreman, F., Vindigni, M., Ius, T., Ghasemian, A., Bonin, S., Skrap, M., Stanta, G. and Vindigni, A. (2011). The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor cell proliferation. Mol. Cancer 10, 83.
• Lucic, B., Zhang, Y., King, O., Mendoza-Maldonado, R., Berti, M., Niesen, F.H., Burgess-Brown, N.A., Pike, A.C.W., Cooper, C.D.O., Gileadi, O. and Vindigni, A. (2010). A prominent b-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation. Nucleic Acids Res. 39, 1703-1717 
• Thangavel, S., Mendoza-Maldonado, R., Tissino, E., Sidorova, J.M., Yin, J., Wang, W., Monnat, R.J., Falaschi, A. and Vindigni, A. (2010). The human RECQ1 and RECQ4 helicases play distinct roles in DNA replication initiation. Mol. Cell. Biol. 30, 1382-1396.
• Xu, D., Muniandy, P., Leo, E., Yin, J., Thangavel, S., Shen, X., Ii, M., Agama, K., Guo, R., Fox, D. 3rd, Meetei, A.R., Wilson, L., Nguyen, H., Weng, N.P., Brill, S.J., Li, L., Vindigni, A., Pommier, Y., Seidman, M. and Wang, W. (2010). Rif1 provides a new DNA-binding interface for the Bloom syndrome complex to maintain normal replication. EMBO J. 29, 3140-3155.
• Vindigni, A., Marino, F. and Gileadi, O. (2010). Probing the structural basis of RecQ helicase function. Biophys. Chem. 149, 67-77.
• Pike, A., Shrestha, B., Popuri, V., Burgess-Brown, N., Muzzolini, L., Costantini, S., Vindigni, A. and Gileadi, O. (2009). Structure of the human RECQ1 helicase: identification of a putative strand-separation pin. Proc. Natl. Acad. Sci. USA 106, 1039-1044.

Alfredo De Biasio

Curriculum vitae: Degree in Chemistry, University of Padua. 2008 PhD in Molecular Genetics and Biotechnology, ICGEB, Trieste, Italy 2008-2009 Postdoctoral Fellow, BIDMC and Harvard Medical School, Boston, USA 2009-2013 Juan de la Cierva Postdoctoral Fellow, CIC bioGUNE, Derio, Spain 2014-2017 Postdoctoral Fellow and AIRC-Marie Curie Fellow, Elettra-Sincrotrone Trieste, Italy 2017-2021 Lecturer, Leicester Institute of Structural and Chemical Biology, University of Leicester, UK 2002-2012 Group Leader, Genome Stability Group, ICGEB, Trieste. Current positions: Assistant Professor, BESE Division, King Abdullah University for Science and Technology (KAUST), Saudi Arabia Honorary Lecturer, Leicester Institute of Structural and Chemical Biology, University of Leicester, UK Young Distinguished Scientist, Elettra-Sincrotrone Trieste, Italy

Contact details: Address: BESE Division, King Abdullah University for Science and Technology (KAUST), Saudi Arabia Email: alfredo.debiasio@gmail.com Webpage: https://www.kaust.edu.sa/en/study/faculty/alfredo-de-biasio

The genetic information is encoded in long chains of deoxyribonucleic acid (DNA) molecules packaged into chromosomes in the cell nucleus. Before dividing, cells need to accurately duplicate their DNA, to ensure that each daughter cell has an identical copy. Critical players in DNA replication are the so-called DNA clamps, ring-shaped proteins that slide on the DNA double helix and anchor DNA polymerases, the enzymes that replicate DNA, to the genomic template. Beside DNA replication, sliding clamps function in the DNA damage response and the maintenance of genome integrity. Due to their central role in cell proliferation, DNA clamps are an important hallmark of tumours, as well as potential drug targets for anti-cancer therapy.
 
Our aim is to unravel the molecular architecture of eukaryotic DNA replication complexes involving DNA sliding clamps, and to shed light on their inner workings. To tackle these composite, supramolecular assemblies we exploit the power of single-particle Cryo-Electron Microscopy (Cryo-EM).
 
In collaboration with Samir Hamdan’s laboratory at KAUST, we have recently determined the Cryo-EM structure of the human holoenzyme that replicates the DNA lagging strand, which includes DNA polymerase δ, primed DNA, PCNA and flap endonuclease 1 (FEN1). We have also determined the structure of the human Pol κ-PCNA-DNA complex, the holoenzyme that replicates DNA through regions of damage.
Current projects are focused on the working principles of the Simian Virus-40 replisome, which makes use of the viral L-Tag helicase and host replication machinery for viral propagation.

Selected publications (*Corresponding author)

• Lancey C., Tehseen M., Takahashi M., Sobhy M.A., Ragan T.J., Crehuet R., Hamdan S.M.* and De Biasio A.* “Cryo-EM structure of Pol k-DNA-PCNA holoenzyme and implications for polymerase switching in DNA lesion bypass” Preprint at https://www.biorxiv.org/content/10.1101/2020.07.10.196956v1and in peer review in Nature Communications       
• Lancey C., Tehseen M., Raducanu V.S., Rashid F., Merino N., Ragan T.J., Savva C., Zaher M.S., Shirbini A., Blanco F.J., Hamdan S.M.* and De Biasio A.* (2020) “Structure of the processive human Pol dholoenzyme”, Nat. Commun. 11: 1109
• De March M., Barrera-Vilarmau S., Crespan E., Mentegari E., Merino N., Gonzalez-Magaña A., Romano-Moreno M., Maga G., Crehuet R., Onesti S., Blanco F.J. and De Biasio A.* (2018) “p15^PAF binding to PCNA modulates the DNA sliding surface” Nucleic Acids Res. 46(18): 9816-9828.
• De March M., Merino N.,Barrera-Vilarmau S., Crehuet R., Onesti S.*, Blanco F.J.* and De Biasio A.* (2017) “Structural basis of human PCNA sliding on DNA” Nat. Commun. 7, 13935 **  [** this paper was reviewed in Yao N. and O'Donnell M. “DNA Replication: How Does a Sliding Clamp Slide?” (2017) Curr. Biol. 27(5):R174-R176]
• De Biasio A.*, Ibañez de Opakua A., Mortuza G., Molina A., Cordeiro T.N., Castillo F., Villate M., Merino N.,Delgado S., Gil-Cartón D., Luque I., Diercks T., Bernadó P., Montoya G. and Blanco F.J.* (2015) “Structure of p15^PAF‒PCNA complex and implications for clamp sliding during DNA replication and repair” Nat. Commun. 6:6439.
   

Recent Publications

* Corresponding author
# Shared first author

2022

Semrau, M. S.; Giachin, G.; Covaceuszach, S.; Cassetta, A.; Demitri, N.; Storici, P.*; Lolli, G.* (2022) Molecular Architecture of the Glycogen- Committed PP1/PTG Holoenzyme. Nat Commun, 13 (1), 6199. https://doi.org/10.1038/s41467-022-33693-z.

Pelliccia, S.; Cerchia, C.; Esposito, F.; Cannalire, R.; Corona, A.; Costanzi, E.; Kuzikov, M.; Gribbon, P.; Zaliani, A.; Brindisi, M.; Storici, P.; Tramontano, E.; Summa, V.  (2022) Easy Access to α-Ketoamides as SARS-CoV-2 and MERS Mpro Inhibitors via the PADAM Oxidation Route. European Journal of Medicinal Chemistry, 114853. https://doi.org/10.1016/j.ejmech.2022.114853.

Balboni, B., Tripathi, S. K., Veronesi, M., Russo, D., Penna, I. ,Giabbai, B., Bandiera, T., Storici, P., Girotto, S.,* Cavalli, A.* (2022) Identification of Novel GSK-3β Hits Using Competitive Biophysical Assays. Int. J. Mol. Sci., 18. https://doi.org/10.3390/ijms23073856.

Demuro, S.; Sauvey, C.; Tripathi, S. K.; Di Martino, R. M. C.; Shi, D.; Ortega, J. A.; Russo, D.; Balboni, B.; Giabbai, B.; Storici, P.; Girotto, S.; Abagyan, R.,* Cavalli, A.* (2022) ARN25068, a Versatile Starting Point towards Triple GSK-3β/FYN/DYRK1A Inhibitors to Tackle Tau-Related Neurological Disorders. European Journal of Medicinal Chemistry, 229, 114054. https://doi.org/10.1016/j.ejmech.2021.114054.

2021

Costanzi, E.#; Kuzikov, M., Esposito, F., Albani, S., Demitri, N., Giabbai, B., Camasta, M., Tramontano, E., Rossetti, G., Zaliani, A., Storici, P.* (2021). Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L. International Journal of Molecular Sciences, 22 (21), 11779. https://doi.org/10.3390/ijms222111779

Brullo C., Rapetti F., Abbate S., Prosdocimi T., Torretta A., Semrau M.S., Massa M., Alfei S., Storici P., Parisini E., Bruno O.* (2021). Design, synthesis, biological evaluation and structural characterization of novel GEBR library PDE4D inhibitors. European Journal of Medicinal Chemistry, 223, 113638. https://doi.org/10.1016/j.ejmech.2021.113638

Gossen J., Albani S., Hanke A., Joseph B. P., Bergh C., Kuzikov M., Costanzi E., Manelfi C., Storici P., Gribbon P., Beccari A. R., Talarico C., Spyrakis F., Lindahl E., Zaliani A., Carloni P., Wade R. C., Musiani F., Kokh D. B. Rossetti G.* (2021). A Blueprint for High Affinity SARS-CoV-2 Mpro Inhibitors from Activity-Based Compound Library Screening Guided by Analysis of Protein Dynamics. ACS Pharmacology & Translational Science, 4(3), 1079–1095. https://doi.org/10.1021/acsptsci.0c00215

Kuzikov M., Costanzi E., Reinshagen J., Esposito F., Vangeel L., Wolf M., Ellinger B., Claussen C., Geisslinger G., Corona A., Iaconis D., Talarico C., Manelfi C., Cannalire R., Rossetti G., Gossen J., Albani S., Musiani F., Herzog K., Ye Y., Giabbai B., Demitri N., Jochmans D., Jonghe S. D., Rymenants J., Summa V., Tramontano E., Beccari A. R., Leyssen P., Storici P., Neyts J., Gribbon P., Zaliani A.* (2021). Identification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen. ACS Pharmacology & Translational Science, 4 (3), 1096–1110. https://doi.org/10.1021/acsptsci.0c00216

Zucchiatti P., Birarda G., Cerea A., Semrau M.S., Hubarevich A.,Storici P., De Angelis F., Toma A., Vaccari L.* (2021). Binding of tyrosine kinase inhibitor to epidermal growth factor receptor: Surface-enhanced infrared absorption microscopy reveals subtle protein secondary structure variations. Nanoscale, 13(16), 7667–7677. https://doi.org/10.1039/d0nr09200b

Annunziato G., Spadini C., Franko N., Storici P., Demitri N., Pieroni M., Flisi S., Rosati L., Iannarelli M., Marchetti M., Magalhaes J., Bettati S., Mozzarelli A., Cabassi C. S., Campanini B., Costantino G.* (2021). Investigational Studies on a Hit Compound Cyclopropane–Carboxylic Acid Derivative Targeting O-Acetylserine Sulfhydrylase as a Colistin Adjuvant. ACS Infectious Diseases, 7(2), 281–292. https://doi.org/10.1021/acsinfecdis.0c00378

Battista T., Pascarella G., Staid D. S., Colotti G., Rosati J., Fiorillo A., Casamassa A., Vescovi A. L., Giabbai B., Semrau M.S., Fanelli S., Storici P., Squitieri F., Morea V., Ilari A.* (2021). Known Drugs Identified by Structure-Based Virtual Screening Are Able to Bind Sigma-1 Receptor and Increase Growth of Huntington Disease Patient-Derived Cells. International Journal of Molecular Sciences, 22(3), 1293. https://doi.org/10.3390/ijms22031293

Ubbiali D., Orlando M., Kovačič M., Iacobucci C., Semrau M.S., Bajc G., Fortuna S., Ilc G., Medagli B., Oloketuyi S., Storici P., Sinz A., Grandori R., de Marco A.* (2021). An anti-HER2 nanobody binds to its antigen HER2 via two independent paratopes. International Journal of Biological Macromolecules, 182, 502–511. https://doi.org/10.1016/j.ijbiomac.2021.04.032

Peleg Y., Vincentelli R., Collins B. M., Chen K.-E., Livingstone E. K., Weeratunga S., Leneva N., Guo Q., Remans K., Perez K., Bjerga G. E. K., Larsen Ø., Vaněk O., Skořepa O., Jacquemin S., Poterszman A., Kjær S., Christodoulou E., Albeck S., Dym, O., Ainbinder E., Unger T., Schuetz, A., Matthes, S., Bader, M., de Marco, A., Storici P., Semrau M.S., Stolt-Bergner P., Aigner C., Suppmann S., Goldenzweig A., Fleishman, S. J. (2021). Community-wide experimental evaluation of the pross stability-design method. Journal of Molecular Biology, 433(13), 166964. https://doi.org/10.1016/j.jmb.2021.166964

Mohammed Khalid A.A., Parisse P.*, Medagli B., Onesti S.*, Casalis L.* (2021). Atomic Force Microscopy investigation of the interactions between the MCM helicase and DNA. Materials. 14, 687.

Bottega R., Ravera S., Napolitano L.M.R., Chiappetta V., Zini N., Crescenzi B., Arniani S., Faleschini M., Cortone G., Faletra F., Medagli B., Sirchia F., Moretti M., de Lange J., Cappelli E., Mecucci C., Onesti S., Pisani F.M., Savoia A.* (2021). Mitochondrial defect in Warsaw syndrome cells genomic integrity and mitochondrial metabolism defects in Warsaw syndrome cells: A comparison with Fanconi anemia. J Cell Physiol. Online ahead of print.

2020

Veggiani G., Giabbai B., Semrau M.S., Medagli B.,Riccio V., Bajc G.,Storici P., de Marco A.* (2020). Comparative analysis of fusion tags used to functionalize recombinant antibodies. Protein Expression and Purification,166, 105505. https://doi.org/10.1016/j.pep.2019.105505

Pachetti M., Marini B., Benedetti F., Giudici F., Mauro E., Storici P., Masciovecchio C., Angeletti S., Ciccozzi M., Gallo R. C., Zella D., & Ippodrino R.* (2020). Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant.Journal of Translational Medicine,18(1), 179. https://doi.org/10.1186/s12967-020-02344-6

Cavalloro V., Russo K., Vasile F, Pignataro L., Torretta A., Donini S., Semrau M.S., Storici P., Rossi D., Rapetti F., Brullo C., Parisini E., Bruno O., Collina S.* (2020). Insight into GEBR-32a: Chiral Resolution, Absolute Configuration and Enantiopreference in PDE4D Inhibition. Molecules, 25(4), 935. https://doi.org/10.3390/molecules25040935

De March M., Onesti S.*, De Biasio A.* (2020) Reply to: "Does PCNA diffusion on DNA follow a rotation-coupled translation mechanism?" Nat. Commun. 11, 4999.

Ullah R., Shehzad A., Ali Shah M., De March M., Ismat F., Iqbal M., Onesti S., Rahman M., McPherson M.J.* (2020). C-Terminal Domain of the Human Zinc Transporter hZnT8 Is Structurally Indistinguishable From Its Disease Risk Variant (R325W). Int J Mol Sci, 21, 926.

2019

Lazzari E., El-Halawany M., De March M., Valentino F., Cantatore F., Migliore C., Onesti S., Meroni G.* (2019). Analysis of the Zn-binding domains of TRIM32, the E3 ubiquitin ligase mutated in Limb Girdle Muscular Dystrophy 2H. Cells, 8, E254.

Bottega R., Napolitano L.M.R., Carbone A., Cappelli E., Corsolini F., Onesti S., Savoia A., Gasparini P., Faletra F.* (2019). Two further patients with Warsaw breakage syndrome. Is a mild phenotype possible? Mol. Genet. Genom. Med. 7, e693.

Gonzalez-Magaña A., Ibáñez de Opakua A., Romano-Moreno M., Murciano-Calles J., Merino N., Luque I., Rojas A.L., Onesti S., Blanco F.J., De Biasio A.* (2019). The p12 subunit of human polymerase δ uses an atypical PIP-box for molecular recognition of proliferating cell nuclear antigen (PCNA). J. Biol. Chem. 294, 3947-3956.

Soler M.A., Medagli B., Semrau M.S., Storici P., Bajc G, de Marco A, Laio A, Fortuna S.* (2019). A consensus protocol for the in silico optimisation of antibody fragments. Chem Commun 19,14043-14046. 
 
Rosa B., Marchetti M., Paredi G., Amenitsch H., Franko N., Benoni R., Giabbai B., De Marino M.G., Mozzarelli A., Ronda L., Storici P.*, Campanini B.*, Bettati S.* (2019). Combination  of SAXS and Protein Painting Discloses the Three-Dimensional Organization of the Bacterial Cysteine Synthase Complex, a Potential Target for Enhancers of Antibiotic Action. Int J Mol Sci.20. pii: E5219. 
 
Gobbo D., Piretti V., Di Martino R.M.C., Tripathi S.K., Giabbai B., Storici P., Demitri N., Girotto S., Decherchi S.,* Cavalli A.* (2019). Investigating Drug-Target Residence Time in Kinases through Enhanced Sampling Simulations. J Chem Theory Comput. 15, 4646-4659. 
 
Redenti S., Marcovich I., De Vita T., Pérez C., De Zorzi R., Demitri N., Perez D.I., Bottegoni G., Bisignano P., Bissaro M., Moro S., Martinez A., Storici P., Spalluto G., Cavalli A.,* Federico S.* (2019). A Triazolotriazine-Based Dual GSK-3β/CK-1δ Ligand as a Potential Neuroprotective Agent Presenting Two Different Mechanisms of Enzymatic Inhibition. ChemMedChem.14, 310-314.

2018

Pisani F.M.*, Napolitano E., Napolitano L.M.R., Onesti S.* (2018). Molecular and Cellular Functions of the Warsaw Breakage Syndrome DNA Helicase DDX11. Genes, 9, 564. 

De March M., Barrera-Vilarmau S., Crespan E., Mentegari E., Merino N., Gonzalez-Magaña A., Romano-Moreno M., Maga G., Crehuet R., Onesti S., Blanco F.J., De Biasio A.* (2018). p15^PAF binding to PCNA modulates the DNA sliding surface. Nucleic Acids Res. 46, 9816-9828.

Napolitano L.M.R., Marchesi A., Rodriguez A., De March M., Onesti S., Laio A.*, Torre V.* (2018). The permeation mechanism of organic cations through a CNG mimic channel. PLoS Comput. Biol. 14, e1006295. 

Caporuscio F., Tinivella A., Restelli V., Semrau M.S., Pinzi L., Storici P., Broggini M., Rastelli G. (2018). Identification of small-molecule EGFR allosteric inhibitors by high-throughput docking. Future Med. Chem. 10, 1545.

Prosdocimi T., Mollica L., Donini S., Semrau M.S., Lucarelli A.P., Aiolfi E., Cavalli A., Storici P., Alfei S., Brullo C., Bruno O., Parisini E.* (2018). Molecular Bases of PDE4D Inhibition by Memory-Enhancing GEBR Library Compounds. Biochemistry. 57, 2876.

Stolt-Bergner P., Benda C., Bergbrede T., Besir H., Celie P.H.N., Chang C., Drechsel D., Fischer A., Geerlof A., Giabbai B., van den Heuvel J., Huber G., Knecht W., Lehner A., Lemaitre R., Nordén K., Pardee G., Racke I., Remans K., Sander A., Scholz J., Stadnik M., Storici P., Weinbruch D., Zaror I., Lua L.H.L., Suppmann S.* (2018). Baculovirus-driven protein expression in insect cells: A benchmarking study.  J. Struct Biol. 203, 71. 

Mazzolini M., Arcangeletti M., Marchesi A., Napolitano L.M.R., Grosa D., Maity S., Anselmi C., Torre V.* (2018). The gating mechanism in cyclic nucleotide-gated ion channels. Scientific Rep. 8, 45.

Carlino L., Christodoulou M.S., Restelli V., Caporuscio F., Foschi F., Semrau M.S., Costanzi E., Tinivella A., Pinzi L., Lo Presti .L, Battistutta R., Storici P., Broggini M., Passarella D., Rastelli G.* (2018). Structure-Activity Relationships of Hexahydrocyclopenta[c]quinoline Derivatives as Allosteric Inhibitors of CDK2 and EGFR. ChemMedChem. 13, 2627-2634. 
 
Raboni S., Revtovich S., Demitri N., Giabbai B., Storici P., Cocconcelli C., Faggiano S., Rosini E., Pollegioni L., Galati S., Buschini A., Morozova E., Kulikova V., Nikulin A., Gabellieri E., Cioni P., Demidkina T., Mozzarelli A.* (2018). Engineering methionine γ-lyase from Citrobacter freundii for anticancer activity. Biochim Biophys Acta Proteins Proteom. 1866, 1260-1270.

2017

De March M., De Biasio A.* (2017). The dark side of the ring: role of the DNA sliding surface of PCNA.  Crit. Rev. Biochem. Mol. Biol. 52, 663.

Campaner E., Rustighi A., Zannini A., Cristiani A., Piazza S., Ciani Y., Kalid O., Golan G., Baloglu E., Shacham S., Valsasina B., Cucchi U., Pippione A.C., Lolli M.L., Giabbai B., Storici P., Carloni P., Rossetti G., Benvenuti F., Bello E., D'Incalci M., Cappuzzello E., Rosato A., Del Sal G.* (2017). Nat. Commun. 8, 15772.

Ali Shah M., Ullah R., De March M., Salahuddin Shaha M., Ismata F., Habib M., Iqbala M., Onesti S., Rahman M.* (2017). Overexpression and characterization of the 100K protein of Fowl adenovirus-4 as an antiviral target. Virus Research 238, 218-225.

Basters A., Geurink P.P., Röcker A., Witting K.F., Tadayon R., Hess S., Semrau M.S., Storici P., Ovaa H., Knobeloch K-P*, and Fritz G.* (2017). Structural basis for the specificity of USP18 towards ISG15. Nat. Struct. & Mol. Biol., 24, 270-278.

Deka J.#, Mojumdar A.#, Parisse P., Onesti S.* and Casalis L.* (2017). DNA-conjugated gold nanoparticles based colorimetric assay to assess helicase activity: a novel route to screen potential helicase inhibitors. Scientific Rep. 7, 44358

De March M., Merino N., Barrera-Vilarmau S., Crehuet R., Onesti S*., Blanco F.S*. and De Biasio A.* (2017). Structural basis of human PCNA sliding on DNA. Nat. Commun. 7, 13935.

Carroni M.#, De March M.#, Medagli B., Krastanova I., Taylor I.A., Amenitsch H., Araki H., Pisani F.M., Patwardhan A. and Onesti S.* (2017). New insights into the GINS complex explain the controversy between existing structural models. Scientific Rep. 7, 40188.

Mojumdar A., De March M., Marino F. and Onesti S.* (2017) The human RecQ4 helicase contains a functional RQC domain that is essential for activity. J. Biol. Chem. 292, 4176-4184.

Cordeiro T.N., Chen P.C., De Biasio A., Sibille N., Blanco F.J., Hub J.S., Crehuet R. and Bernadó P.* (2017). Disentangling polydispersity in the PCNA-p15PAF complex, a disordered, transient and multivalent macromolecular assembly. Nucleic Acids Res. 45, 1501-1515.

2016

Ormaza G., Medagli B., Rodríguez J.A., Ibáñez de Opakua A., Merino N., Villate M., Onesti S. and Blanco F.J.* (2016). The tumor suppressor ING4 binds double stranded DNA with micromolar affinity through its disordered central region. FEBS Letters. 591, 425-432.

Kenig S.*, Faoro V., Bourkoula E., Podergajs N., Ius T., Vindigni M., Skrap M., Lah T., Cesselli D., Storici P., Vindigni A. (2016). Topoisomerase IIβ mediates the resistance of glioblastoma stem cells to replication stress-inducing drugs. Cancer Cell Int.16, 58.

Medagli B., Di Crescenzio P., De March M. and Onesti S.* (2016). Structure and activity of the Cdc45-Mcm2-7-GINS (CMG) complex, the replication helicase. (Chapter in "The initiation of DNA replication in eukaryotes", Ed. D. Kaplan, Springer).

Marino F.#, Mojumdar A.#, Zucchelli C. Bhardwaj A., Buratti E., Vindigni A., Musco G. and Onesti S.* (2016). Structural and biochemical characterization of an RNA/DNA binding motif in the N-terminal domain of RecQ4 helicases. Scientific Rep. 6, 21501.
 

2015

Iseppon F., Napolitano L.M.R., Torre V. and Cojoc D.* (2015). Cdc42 and RhoA reveal different spatio-temporal dynamics upon local stimulation with Semaphorin 3-A. Front. Cell. Neurosc. 9, 333.

Kenig S.*, Bedolla D.E., Birarda G., Faoro V., Mitri E., Vindigni A., Storici P. and Vaccari L. (2015). Fourier transform infrared microspectroscopy reveals biochemical changes associated with glioma stem cell differentiation. Biophys Chem. 207, 90-96.

Ronda L., Bruno S., Bettati S., Storici P., Mozzarelli A.* (2015)  From protein structure to function via single crystal optical spectroscopy. Front Mol Biosci 28, 2-12. 

Gianoncelli A., Vaccari L.*, Kourousias G., Cassese D., Bedolla D.E., Kenig S., Storici P., Lazzarino M., Kiskinova M. (2015) Soft X-Ray Microscopy Radiation Damage ON Fixed Cells Investigated with Synchrotron Radiation FTIR Microscopy. Scientific Rep. 5,10250. 

Napolitano L.M.R., Bisha I., De March M., Marchesi A., Arcangeletti M., Demitri N., Mazzolini M., Rodriguez A., Magistrato A., Onesti S.*, Laio A.* and Torre V.* (2015). A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels. Proc. Natl. Acad. Sci. USA. 112, E3619-E3628. 

De March M., Brancatelli G., Demitri N., De Zorzi R., Hickey N., Geremia S.* (2015). A general exit strategy of monoheme cytochromes c and c2 in electron transfer complexes? IUBMB Life 67, 694-700

Lausi A.*, Polentarutti M., Onesti S., Plaisier J.R., Busetto E., Bais G., Barba L., Cassetta A., Campi G., Lamba D., Pifferi A., Mande S.C., Sarma D.D., Sharma S.M., Paolucci G. (2015). Status of the crystallography beamlines at Elettra. Eur. Phys. J. Plus 130, 43-51.

De Biasio A.*, de Opakua A.I., Mortuza G.B., Molina R., Cordeiro T.N., Castillo F., Villate M., Merino N., Delgado S., Gil-Cartón D., Luque I., Diercks T., Bernadó P., Montoya G., Blanco F.J. (2015). Structure of p15(PAF)-PCNA complex and implications for clamp sliding during DNA replication and repair. Nat Commun. 6:7439. 

Pike A.C., Gomathinayagam S., Swuec P., Berti M., Zhang Y., Schnecke C., Marino F., von Delft F., Renault L., Costa A., Gileadi O., Vindigni A.* (2015). Human RECQ1 helicase-driven DNA unwinding, annealing, and branch migration: Insights from DNA complex structures. Proc. Natl. Acad. Sci. USA. 112, 4286-4291.

Cersosimo U., Sgorbissa A., Foti C., Drioli S., Angelica R., Tomasella A., Picco R., Semrau M., Storici  P., Benedetti F., Berti F.*, Brancolini C.* (2015)  Synthesis, Characterization and Optimization for in Vivo Delivery of a Non-Selective Isopeptidase Inhibitor as New Anti-Neoplastic Agent.  J.Med.Chem. 26;58(4):1691-704.

De March M., Di Rocco G., Hickey N., Geremia S.* (2015). High-resolution crystal structure of the recombinant diheme cytochrome c from Shewanella baltica (OS155). J Biomol. Struct. Dyn. 33, 395-403.

2014

De Biasio A., Ibáñez de Opakua A., Cordeiro T.N., Villate M., Merino N., Sibille N., Lelli M., Diercks T., Bernadó P., Blanco F.J.* (2014). p15PAF is an intrinsically disordered protein with nonrandom structural preferences at sites of interaction with other proteins. Biophys J. 106, 865-874.

De March M., Demitri N., De Zorzi R., Casini A., Gabbiani C., Guerri A., Messori L., Geremia S.* (2014). Nitrate as a probe of cytochrome c surface: crystallographic identification of crucial "hot spots" for protein-protein recognition. J Inorg Biochem. 135, 58-67.

Bedolla D., Kenig S., Mitri E., Storici P., Vaccari L.* (2014) Further insights into G1 and G0 phases of cell cycle revealed by FTIR microspectroscopy. Vib. Spec. 75: 127-135. DOI: 10.1016/j.vibspec.2014.08.007 .

Wiedemann C., Ohlenschläger O., Medagli B., Onesti S. and Görlach M.* (2014). ¹H,  ¹⁵N and ¹³C chemical shift assignments for the winged helix domains of two archeal MCM C-termini. Biomol NMR Assign. 8, 357-360. 

Mitri E., Birarda G., Vaccari L., Kenig S., Tormen M., Grenci G.* (2014). SU-8 bonding protocol for the fabrication of microfluidic devices dedicated to FTIR microspectroscopy of live cells. Lab Chip. 138, 4015-4021.

2013

Bedolla D.E., Kenig S., Mitri E., Ferraris P., Marcello A., Grenci G., Vaccari L.* (2013). Determination of cell cycle phases in live B16 melanoma cells using IRMS. Analyst. 138, 4015-4021

Marino F., Vindigni A. and Onesti S.* (2013). Bioinformatic analysis of RecQ4 helicases reveals the presence of a RQC domain and a Zn knuckle. Biophys Chem. 177-178, 34-39. 

Medagli B. and Onesti S.* (2013). Structure and mechanism of hexameric helicases. Adv. Exp. Med. Biol. 767, 75-95 (Chapter in "DNA helicases and DNA motor proteins", Ed. M. Spies, Springer).

Berti M., Chaudhuri A.R., Thangavel S., Gomathinayagam S., Kenig S., Vujanovic M., Odreman F., Glatter T., Graziano S., Mendoza-Maldonado R., Marino F., Lucic B., Biasin V., Gstaiger M., Aebersold R., Sidorova J.M., Monnat R.J. Jr, Lopes M. and Vindigni A.* (2013). Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition. Nat Struct Mol Biol. 20, 347-354.

Onesti S. and MacNeill S.A.* (2013) Structure and evolutionary origins of the CMG complex. Chromosoma. 122, 47-53.

2012

Parisse, P., Vindigni, A., Scoles, G. and Casalis, L.* (2012). In vitro enzyme comparative kinetics: unwinding of surface-bound DNA nanostructures by RecQ and RecQ1. J. Phys. Chem. Letters, 3, 3532-3537.

Krastanova I., Sannino V., Amenitsch H., Gileadi O., Pisani F.M. and Onesti S.* (2012). Structural and functional insights into the DNA replication factor Cdc45 reveal an evolutionary relationship to the DHH family of phosphoesterases. J. Biol. Chem. 287, 4121-4128.

De March, M., Demitri, N., Geremia, S., Hickey, N. and Randaccio, L.* (2012). Trans and cis influences and effects in cobalamins and in their simple models. J. inorg. biochem. 116, 215-227.

2011

Mendoza-Maldonado, R., Faoro, V., Bajpai, S., Berti, M., Odreman, F., Vindigni, M., Ius, T., Ghasemian, A., Bonin, S., Skrap, M., Stanta, G. and Vindigni, A.* (2011). The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor cell proliferation. Mol. Cancer 10, 83.

2010

Vindigni, A., Marino, F. and Gileadi, O.* (2010). Probing the structural basis of RecQ helicase function. Biophys. Chem. 149, 67-77.

Bindi S., Fancelli D., Alli C., Berta D., Bertrand J.A., Cameron A.D., Cappella P., Carpinelli P., Cervi G., Croci V., D'Anello M., Forte B., Giorgini M.L., Marsiglio A., Moll J., Pesenti E., Pittalà V., Pulici M., Riccardi-Sirtori F., Roletto F., Soncini C., Storici P., Varasi M., Volpi D., Zugnoni P. and Vianello P.* (2010). Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable antitumor activity. Bioorg Med Chem. 18, 7113-7120.

Beria I., Ballinari D., Bertrand J.A., Borghi D., Bossi R.T., Brasca M.G., Cappella P., Caruso M., Ceccarelli W., Ciavolella A., Cristiani C., Croci V., De Ponti A., Fachin G., Ferguson R.D., Lansen J., Moll J.K., Pesenti E., Posteri H., Perego R., Rocchetti M., Storici P., Volpi D. and Valsasina B.* (2010). Identification of 4,5-Dihydro-1H-pyrazolo[4,3-h]quinazoline Derivatives as a New Class of Orally and Selective Polo-Like Kinase 1 Inhibitors. J Med Chem. 53, 3532-3551.

2009

Pike, A., Shrestha, B., Popuri, V., Burgess-Brown, N., Muzzolini, L., Costantini, S., Vindigni, A. and Gileadi, O.* (2009). Structure of the human RECQ1 helicase: identification of a putative strand-separation pin. Proc. Natl. Acad. Sci. USA 106, 1039-1044.

Costa A. and Onesti S.* (2009). Structural biology of MCM helicases. Crit. Rev. Biochem. Mol. Biol. 44, 326-342.

BaeB.,  Chen Y.-H., Costa A., Onesti S., Brunzelle J.S., Lin Y., Cann I.K.O.and Nair S.K.* (2009) Crystal Structure of an Archaeal MCM Homolog Provides Insights into the Architecture of the Replicative Helicase. Structure 17, 211-222.

Jenkinson, E.R., Costa A., Leech, A.P., Patwardhan A., Onesti S. and Chong, J.P* (2009). Mutations in sub-domain B of the MCM helicase affect DNA binding and modulate conformational transitions. J. Biol. Chem. 284, 5654-5661.
 

Funding

Horizon 2020 (MarieSkłodowska-Curie actions) H2020-MSCA-ETN (ITN) 2019 Grant to Silvia Onesti and Luisa Napolitano (Grant Agreement: 859853): "AntiHelix - DNA helicases in genome maintenance: from molecular and cellular mechanisms to specific inhibitors as potential drugs".

French Muscular Dystrophy Association (AFM Téléthon) Grant to Germana Meroni (CBM) and Silvia Onesti: "Structure and function of TRIM32, the ubiquitin ligase mutated in Limb Girdle Muscular Dystrophy 2H".

Programma per la Cooperazione Transfrontaliera Italia-Slovenia Progetto Standard "TRANSGLIOMA:  Searching for novel glioblastoma therapies through a translational and transnational platform" finanziato nell'ambito del Programma per la Cooperazione Transfrontaliera e Italia-Slovenia 2014-2020, to Silvia Onesti e Paola Storici.   Progetto Standard "GLIOMA: identificazione di nuovi marcatori di cellule staminali tumorali a scopo diagnostico e terapeutico" finanziato nell'ambito del Programma per la Cooperazione Transfrontaliera Italia-Slovenia 2007-2013 (Bando pubblico per progetti standard n. 02/2009), to Alessandro Vindigni.   Progetto Standard "PROTEO: Il centro transfrontaliero per lo studio di proteine per la ricerca e la diagnostica oncologica" finanziato nell'ambito del Programma per la Cooperazione Transfrontaliera Italia-Slovenia 2007-2013 (Bando pubblico per progetti standard – risorse dedicate alle aree di confine terrestre n. 03/2011), to Paola Storici, Silvia Onesti and Loredana Casalis.

Regione Friuli Venezia Giulia Progetto DAGEAS to Maurizio Polentarutti e Doriano Lamba: " Realizzazione di una Piattaforma Tecnologica Regionale per la cristallizazione e l'analisi cristallografica di proteine di interesse biomedico."