Paolo Plevani
Paolo Plevani
affiliation: Università di Milano
research area(s): Molecular Biology, Genetics And Genomics
Course: Biomolecular Sciences
University/Istitution: Università di Milano
After the PhD in Biophysics and Molecular Biology at the University of Pavia, Italy he spent 3 years post-doctoral training in US, first at the University of Connecticut at Farmington and then at the USUHS, Bethesda, Maryland working on the mechanisms controlling initiation of DNA replication in eukaryotic cells. After 4 years as a Research Associate at the University of Brescia he became University Researcher and then Associate and Full Professor of Molecular Biology at the University of Milano where he is presently working at the Dept. of Scienze Biomolecolari e Biotecnologie. From 2007 he is the Director of the PhD School in Scienze Biologiche e Molecolari. In his scientific career he coordinated several national and international research program and he is acting as evaluator and chairman in various Marie Curie European Union actions.
Paolo Plevani"s major research interests are the molecular mechanisms of DNA replication and repair and their connections with the checkpoints controlling cell cycle progression under normal and pathological conditions. His laboratory contributed to the identification and characterization of new checkpoint genes and developed a number of genetic and biochemical approaches to improve our understanding of the checkpoint mechanisms and their cross-talks with other DNA transactions. Since several years he is also exploiting the use of model systems, in particular yeast cells, to better understand at the molecular level the mechanism of cancerogenesis and other human pathologies. He is author of ~ 100 publications on well recognized peer-reviewed international journals.
Lazzaro F., Giannattasio M., Puddu F., Granata M., Pellicioli A., Plevani P.* and Muzi-Falconi M.* (2009) Checkpoint mechanisms at the intersection between DNA damage and repair. DNA Repair, 8, 1055-1067. *Corresponding authors
Diani, L., Colombelli, C., Tamilselvan Nachimuthu, B., Donnianni, R., Plevani, P., Muzi-Falconi, M. and Pellicioli, A. (2009) Saccharomyces Cdk1 phosphorylates checkpoint kinase Rad53 in metaphase influencing cellular morphogenesis. J. Biol. Chem., 284, 32627-32634.
Ward, J., D., Muzzini, D. M., Petalcorin, M. I. R., Martin-Perez, E., Martin, J. S., Plevani, P., Cassata, G., Marini, F., Boulton, S. J. (2010) Overlapping mechanisms promote post-synaptic Rad-51 filament disassembly during meiotic double-strand break repair. Mol. Cell, 37, 259-272.
Donnianni, R., Ferrari, M., Lazzaro, F., Clerici, M., Nachimuthu, B. T., Plevani, P., Muzi-Falconi, M. and Pellicioli, P. (2010) Elevated Levels of the polo kinase Cdc5 override the Mec1/ATR checkpoint in budding yeast by acting at different steps of the signaling pathway. PLoS Genet., 6(1):e1000763.doi:10.1371/journal.pgen.1000763
DiBella, D., Lazzaro, F., Brusco, A., Plumari, M., Battaglia, G., Pastore, A., Finardi, A., Cagnoli, C., Tempia, F., Frontali, M., Veneziano, L., Sacco, T., Boda, E., Brussino, A., Bonn, F., Castellotti, B., Baratta, S., Mariotti, C., Gellera, C., Fracasso, V., Magri, S., Langer, T., Plevani, P., DiDonato, S., Muzi-Falconi, M. and Taroni, F. (2010) Mutations in the mitochondrial protease AFG3L2 cause dominant hereditary ataxia SCA28. Nature Gen., 42, 313-321.
Granata, M., Lazzaro, F., Novarina, D., Panigada, D., Puddu, F., Abreu, C.M., Kumar, R., Grenon, M., Lowndes, N.F., Plevani, P.* and Muzi-Falconi, M.* (2010) Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by its Dimerization and Are Cell Cycle Regulated by CDK1 Activity. PLoS Genet., 6(8):e10010.47.doi:10.1371/journal.pgen.1001047 * Corresponding authors.
Giannattasio, M., Follonier, C., Tourriére, H., Puddu, F., Lazzaro, F., Pasero, P., Lopes, M., Plevani, P.* and Muzi-Falconi, M.* (2010) Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps and promotes checkpoint activation. Mol. Cell, 40, 50-62. * Corresponding authors
Tumini, E., Plevani, P., Muzi-Falconi, M. and Marini, F. (2011) Physical and functional crosstalk between Fanconi anemia core components and the GINS replication complex. DNA repair, 10, 149-158.
Puddu, F., Piergiovanni, G., Plevani, P.* and Muzi-Falconi, M.* (2011) Sensing of replication stress and Mec1 activation act through two independent pathways involving the 9-1-1 complex and DNA polymerase ε. PloS Genet., 7(3): e1002022. doi:10.1371/journal.pgen.1002022 * Corresponding authors
Novarina, D., Amara, F., Lazzaro, F., Plevani, P.* and Muzi-Falconi, M.* (2011) Mind the gap: keeping UV lesions in check. DNA repair (in press) * Corresponding authors
Sertic, S., Pizzi, S., Cloney, R., Lehmann, A.R., Marini, F., Plevani, P.* and Muzi-Falconi, M.* (2011) Human Exonuclease 1 connects NER processing with checkpoint activation in response to UV irradiation. Proc. Natl. Acad. Sci. USA, (in press). * Corresponding authors.
Project Title:
Role of RNaseH and of the Post-Replication Repair pathways in protecting cells from rNTPs misincorporation during DNA replication.
We gained evidence in yeast that S.cerevisiae cells need both RNaseH1 and RNaseH2 to remove rNTPs misincorporated during DNA replication. Cells normally survive to rNMPs misincorporated in DNA by using the two Post-Replication Repair (PRR) sub-pathways (translesion DNA synthesis and template swithcing) (Lazzaro et al., submitted). We wish to learn more on the molecular mechanisms linking rNTPS misincorporation and PRR using yeast cells as a model system and to extend this analysis to human cells. Indeed it has been found that mutations in the human RNaseH2 gene are linked to the Aicardi-Goutieres syndrome whose pathogenetic mechanisms are still unknown.