Research Groups
Genome Stability
Research Interests and Description
Research Interests
DNA repair, genomic instability, RecQ helicases, proteomics.
Description of Research
Our Group investigates the enzymatic activity and function of RecQ helicases. RecQ helicases have attracted considerable interest in recent years, not only because of their role in the maintenance of chromosome stability, but also for their connection to disorders associated with cancer predisposition and premature aging. In particular, we have discovered that different oligomeric forms of RECQ1 are associated with distinct enzymatic activities and have collaborated on the resolution of the first crystal structure of a truncated form of the protein proficient in DNA unwinding. We have also highlighted several differences between the substrate specificities of RECQ1, BLM, and WRN, providing a strong indication that these helicases are likely to perform non-overlapping functions in cells. Recently, we have concentrated our efforts on the analysis of the different the roles of RecQ helicases in DNA replication. Our studies have provided new insight into the distinct functions of the human RecQ helicases in DNA replication by defining important and distinct roles of RECQ1 and RECQ4 during this process. Consistent with its proposed role in DNA replication, we have discovered that RECQ1 is highly expressed in glioblastoma cells and plays an important role in tumour cell proliferation suggesting that RECQ1 might represent a new suitable target for anti cancer therapies aimed to arrest cell proliferation in brain gliomas.
Recent Publications
Mendoza-Maldonado, R., Faoro, V., Bajpai, S., Berti, M., Odreman, F., Vindigni, M., lus, T., Ghasemian, A., Bonin, S., Skrap, M., Stanta, G., 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 PubMed link
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., Vindigni, A. A prominent b-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation. Nucleic Acids Res. In press PubMed link
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
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
