Research Groups

Genome Stability

Group Leader

Research Interests and Description
Group Members

Alessandro Vindigni

International Centre for Genetic Engineering and Biotechnology
Padriciano 99
34012 Trieste, Italy

E-mail: vindigni@icgeb.org
Office tel: +39-040-3757369
Lab tel: +39-040-3757326
Office fax: +39-040-226555

Education

University of Padua, Padua, Italy, Degree in Chemistry, 1992
University of Padua, Padua, Italy, PhD in Biochemistry and Molecular Biophysics, 1995

Career History

Since 2002, Group Leader of the Genome Stability Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
1999-2002, Staff Scientist, Molecular Biology Group, ICGEB, Trieste, Italy.
1995-1999, Postdoctoral fellow, Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
1994-1995, PhD student, Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
1992-1994, PhD student, CRIBI Biotechnology Centre, University of Padua, Padua, Italy.
1991-1992, Undergraduate student, CRIBI Biotechnology Centre, University of Padua, Italy.
1990, ERASMUS exchange student, Chemistry Dept., University of Newcastle upon Tyne, England.

Honors
1996-1998, American Heart Association Postdoctoral Fellowship.
1995-1996, W.M. Keck Fellowship, Washington University School of Medicine.

Teaching Activity

2009, co-organizer of the ICGEB Workshop on “Proteomic Characterization of Macromolecular Complexes Involved in DNA Metabolism”, Trieste, Italy.
2008, co-organizer of the ICGEB Theoretical and Practical Course entitled “Proteomic Approaches in Molecular Biology: Theory and Practice”, Buenos Aires, Argentina.
Since 2003, external Professor of Proteomics, Faculty of Medicine, University of Trieste, Italy.
Since 2003, DNA repair course for the 1st year PhD candidates of the Open University/Scuola Normale Superiore at ICGEB, Trieste, Italy.

Scientific Activity

The Group is interested in the characterization of the enzymatic activity and function of enzymes involved in DNA damage and repair. In particular, we now focus on RecQ helicases. A combination of biochemical, proteomic, and structural approaches is used to shed light on the function of these helicases in the maintenance of genome integrity. Moreover, we are also interested in DNA non-homologous end-joining (NHEJ), one of the two major mechanisms of double strand break repair in cells.

Selected publications

Thangavel, S., Mendoza-Maldonado, R., Tissino, E., Sidorova, J.M., Yin, J., Wang, W., Monnat, R.J., Falaschi, A., Vindigni, A. 2010. The human RECQ1 and RECQ4 helicases play distinct roles in DNA replication initiation. Mol. Cell. Biol. 30, 1382-1396 PubMed link

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., Wang, W. 2010. Rif1 provides a new DNA-binding interface for the Bloom syndrome complex to maintain normal replication. EMBO J. 29, 3140-3155 PubMed link

Vindigni, A., Marino, F., Gileadi, O. 2010. Probing the structural basis of RecQ helicase function. Biophys. Chem. 149, 67-77 PubMed link

Vindigni, A., Hickson, I.D. 2009. RecQ helicases: multiple structures for multiple functions? HFSP Journal 3, 153-164 PubMed link

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

Smith, E., Dejsuphong, D., Balestrini, A., Hampel, M., Lenz, C., Vindigni, A., Costanzo, V. 2009. An ATM and ATR dependent checkpoint inactivates spindle assembly by targeting CEP63. Nat. Cell Biol. 11, 278-285 PubMed link

Kusumoto, R., Dawut, L., Marchetti, C., Wan Lee, J., Vindigni, A., Ramsden, D., Bohr, V.A. 2008. Werner protein cooperates with the XRCC4-DNA ligase IV complex in end-processing. Biochemistry 47, 7548-7556

Milli, A., Cecconi, D., Campostrini, N., Timperio, A.M., Zolla, L., Righetti, S.C., Zunino, F., Perego, P., Benedetti, V., Gatti, L., Odreman, F., Vindigni, A., Rigetti, P.G. 2008. A proteomic approach for evaluating the cell response to a novel histone deacetylase inhibitor in colon cancer cells. Biochim. Biophys. Acta 1784, 1702-1710

Popuri, V., Bachrati, C.Z., Muzzolini, L., Mosedale, G., Costantini, S., Giacomini, E., Hickson, I.D., Vindigni, A. 2008. The human RecQ helicases, BLM and RECQ1, display distinct DNA substrate specificities. J. Biol. Chem. 283, 17766-17776

Amiard, S., Doudeau, M., Pinte, S., Poulet, A., Lenain, C., Faivre-Moskalenko, C., Angelov, D., Hug, N., Vindigni, A., Bouvet, P., Paoletti, J., Gilson, E., Giraud-Panis, MJ. 2007. A topological mechanism for TRF2-enhanced strand invasion. Nat. Struct. Mol. Biol. 14,147-154

Costantini, S., Woodbine, L., Andreoli, L., Jeggo, P.A., Vindigni, A. 2007. Interaction of the Ku heterodimer with the DNA ligase IV/Xrcc4 complex and its regulation by DNA-PK. DNA Repair 6, 712-722

Muzzolini, L., Beuron, F., Patwardhan, A., Popuri, V., Cui, S., Niccolini, B., Rappas, M., Freemont, P.S., Vindigni, A. 2007. Different Quaternary Structures of Human RECQ1 Are Associated with its Dual Enzymatic Activity. PLoS Biology, 5, e(20)

Nijnik, A., Woodbine, L., Marchetti, C., Dawson, S., Lambe, T., Liu, C., Rodrigues, N.P., Crockford, T.L., Cabuy, E., Vindigni, A., Enver, T., Bell, J.I., Slijepcevic, P., Goodnow, C.C., Jeggo, P.A., Cornall, R.J. 2007. DNA repair is limiting for haematopoietic stem cells during ageing. Nature 447, 686-690

Vindigni, A. 2007. Biochemical, biophysical, and proteomic approaches to study DNA helicases. Mol. Biosyst. 3, 266-274

Marchetti, C., Walzer, S.A., Odreman, F., Vindigni, A., Doherty, A.J., Jeggo, P. 2006. Identification of a novel motif in DNA ligases exemplified by DNA ligase IV. DNA Repair 5, 788-798

Pozzi Mucelli, S., Odreman, F., Lujardo Gonzales, M., Gerardi, E., Stanta, G., Vindigni, A. 2006. Proteomic studies on the white matter of human brain. J. Chromatogr. B 833, 80-90

Odreman, F., Vindigni, M., Lujardo Gonzales, M., Niccolini, B., Candiano, G., Zanotti, B., Skrap, M., Pizzolitto, S., Stanta, G., Vindigni, A. 2005. Proteomic studies on low- and high-grade human brain astrocytomas. J. Proteome Res. 4, 698-708

Wu, L., Chan, K.L., Ralf, C., Bernstein, D.A., Garcia, P.L., Bohr, V.A., Vindigni, A., Janscak, P., Keck, J.L., Hickson, I.D. 2005. The HRDC domain of BLM is required for the recognition, processing and dissolution of double Holliday junctions. EMBO J. 24, 2679-2687

Sharma, S., Sommers, J.A., Choudhary, S., Faulkner, J.K., Cui, S., Muzzolini, L., Andreoli, L., Vindigni, A., Brosh Jr., R.M. 2005. Biochemical analysis of the DNA unwinding and strand annealing activities catalyzed by human RECQ1, J. Biol. Chem. 280, 28072-28084

Doherty, K.M., Sharma, S., Uzdilla, L.A., Wilson, T.M., Cui, S., Muzzolini, L., Vindigni, A., Brosh Jr., R.M. 2005. RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination. J. Biol. Chem. 280, 28085-28094

Arosio, D., Costantini, S., Kong, Y., Vindigni, A. 2004. Fluorescence anisotropy studies of the Ku-DNA interaction: anion and cation effects. J. Biol. Chem. 279, 42826-42835

Cui, S., Arosio, D., Doherty, K.M., Brosh, R.M. Jr., Falaschi, A., Vindigni, A. 2004. Analysis of the unwinding activity of the dimeric RECQ1 helicase in the presence of human replication protein A. Nucleic Acids Res. 32, 2158-2170

Cui, S., Klima, R., Ochem, A., Arosio, D., Falaschi, A., Vindigni, A. 2003. Characterization of the DNA-unwinding activity of human RECQ1, a helicase specifically stimulated by human replication protein A. J. Biol. Chem. 278, 1424-1432

Arosio, D., Cui, S., Ortega, C., Chovanec, M., Di Marco, S., Baldini, G., Falaschi, A., Vindigni, A. 2002. Studies on the mode of Ku interaction with DNA. J. Biol. Chem. 277, 9741-9748

Vindigni, A. 1999. Energetic Dissection of Specificity in Serine Proteases. Combinatorial Chemistry and High Throughput Screening 2, 125-139.

Ido, Y., Vindigni, A., Chang, K., Di Cera, E., Williamson, J.R. 1997. C-peptide Prevents Vascular and Neural Dysfunction in Diabetic Rats. Science 277, 563-566

Vindigni, A., Dang, Q.D., Di Cera, E. 1997. Site-specific dissection of substrate recognition by thrombin. Nature Biotechnol. 15, 891-895