Research


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 knuckleBiophys 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.

 

Last Updated on Friday, 23 September 2022 23:49