Research Groups
Proteomics
Research Interests and Description
Group Leader: Alessandro Vindigni, PhDGroup Members
Research Interests
DNA repair, genomic instability, RecQ helicases, proteomics.
Description of Research
RecQ helicases are a family of DNA unwinding enzymes required to guard genome stability in all kingdoms of life. Disorders associated with premature aging and/or increased incidence of cancer arise from mutations affecting different members of the RecQ family. The Group investigates the enzymatic activity and function of the human RecQ helicases. We focus on RECQ1, the first RecQ helicase discovered in humans, but also one of the less characterized in terms of enzymatic activity and function. Some RecQ enzymes, in addition to unwinding DNA like a conventional helicase, can also catalyze the annealing of complementary strands. The lab found that two different sizes of RECQ1 multimers are responsible for these two opposite activities and that the equilibrium between the two assembly states is controlled by ATP binding. Based on these findings, we apply a combination of biochemical and structural techniques to further characterize the two oligomeric forms of RECQ1 and elucidate the function of its dual enzymatic activity. Meanwhile, proteomic approaches are employed to describe protein complexes containing RECQ1, whilst experiments with human RECQ1 depleted cells are performed to test the function of RECQ1 and its newly discovered binding partners in vivo.The Group is also interested in DNA non-homologous end-joining (NHEJ) and in the analysis of the protein expression profiles of human brain astrocytomas. NHEJ is one of the two major mechanisms of double strand break repair in cells. The lab investigates the order of assembly and the macromolecular interactions of the NHEJ proteins at the broken DNA ends, and search for novel factors that might be required for the repair process. The Group's work on brain astrocytomas aims at the identification of novel bio-markers for a more accurate classification of tumor grade. The studies allowed the identification of a number of proteins differentially expressed between the indolent low-grade and the highly infiltrating high-grade form of the tumor, also known as glioblastoma multiforme.
Recent Publications
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, 7548-7556Popuri, 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
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 Biol., 5, e20
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
