Paola Perucca
e-mail: paola.perucca AT unipv.it
affiliation: Department of Molecular Medicine, UNIPV
research area(s): Cancer Biology, Experimental Medicine
Course:
Genetics, Molecular and Cellular Biology
University/Istitution: Università di Pavia
University/Istitution: Università di Pavia
ACADEMIC POSITION
Researcher
(MED04) General Pathology
Department of Molecular Medicine, Unit of Immunology and General Pathology, Faculty of Medicine and Surgery, University of Pavia,
Via Ferrata 9, 27100 Pavia, Italy.
Tel. (office) +39 0382-986857
Tel. (lab) +39 0382-986338
Fax: +39 0382-986893
e-mail: paola.perucca@unipv.it
PROFESSIONAL EXPERIENCE
From 2015 – Professor and Member of the Board in Post-Graduate School of Clinical Biochemistry.
From 2013 – Professor and Member of the Board of the Post-Graduate School in Clinical Pathology
From 2011 – Member of the Academic board of the PhD course "Genetica, Biologia Molecolare e Cellulare".
2009-2010 –"Visiting scientist" at the Spanish National Cancer Research Centre (CNIO), of Madrid (E).
Since December 2008 – Researcher of General Pathology (MED/04), Department of Experimental Medicine, General Pathology, University of Pavia, Italy.
2007 - Post Ph.D. (MED/04), Department of Experimental Medicine, General Pathology, University of Pavia, Italy.
2006 – “Cultore della materia” in General Pathology (MED/04), Faculty of Medicine and Surgery, University of Pavia, Italy.
2004 – “Cultore della materia” in General Pathology (MED/04), Faculty of Mathematical, Physical and Natural Science, Biological Sciences, University of Pavia, Italy.
2002-2006 – Post PhD (MED/04), Department of Experimental Medicine, General Pathology, University of Pavia, Italy.
2003 - Ph.D. in Experimental Pathology, Department of Experimental Medicine, General Pathology, University of Pavia, Italy.
2000 - State examination of Biology
1999 - Graduates in Biological Sciences, University of Pavia, Italy
Technology transfer
2013 - Application for the patent registration entitled: “Metodo per la previsione e la rilevazione delle allergie” - “Method for the allergies prediction and detection”.
Number of application: MI2013A001094
Researcher
(MED04) General Pathology
Department of Molecular Medicine, Unit of Immunology and General Pathology, Faculty of Medicine and Surgery, University of Pavia,
Via Ferrata 9, 27100 Pavia, Italy.
Tel. (office) +39 0382-986857
Tel. (lab) +39 0382-986338
Fax: +39 0382-986893
e-mail: paola.perucca@unipv.it
PROFESSIONAL EXPERIENCE
From 2015 – Professor and Member of the Board in Post-Graduate School of Clinical Biochemistry.
From 2013 – Professor and Member of the Board of the Post-Graduate School in Clinical Pathology
From 2011 – Member of the Academic board of the PhD course "Genetica, Biologia Molecolare e Cellulare".
2009-2010 –"Visiting scientist" at the Spanish National Cancer Research Centre (CNIO), of Madrid (E).
Since December 2008 – Researcher of General Pathology (MED/04), Department of Experimental Medicine, General Pathology, University of Pavia, Italy.
2007 - Post Ph.D. (MED/04), Department of Experimental Medicine, General Pathology, University of Pavia, Italy.
2006 – “Cultore della materia” in General Pathology (MED/04), Faculty of Medicine and Surgery, University of Pavia, Italy.
2004 – “Cultore della materia” in General Pathology (MED/04), Faculty of Mathematical, Physical and Natural Science, Biological Sciences, University of Pavia, Italy.
2002-2006 – Post PhD (MED/04), Department of Experimental Medicine, General Pathology, University of Pavia, Italy.
2003 - Ph.D. in Experimental Pathology, Department of Experimental Medicine, General Pathology, University of Pavia, Italy.
2000 - State examination of Biology
1999 - Graduates in Biological Sciences, University of Pavia, Italy
Technology transfer
2013 - Application for the patent registration entitled: “Metodo per la previsione e la rilevazione delle allergie” - “Method for the allergies prediction and detection”.
Number of application: MI2013A001094
NATURAL ANTIOXIDANTS. The biological activity of some natural antioxidants using molecular biology and flow citometry methods was studied. In particular, she demonstrated the antiproliferative effect of some anthocyanins and resveratrol, a phytoalexin present in the red wine, both in normal and tumor cell lines. She evidenced that the molecular mechanisms underlying their antiproliferative properties are different depending on distinct pathways activated from cells in the presence of these compounds. In fact, anthocyanins, and in particular delphinidin, show an apoptotic effect and, finally, resveratrol strongly inhibits DNA synthesis in growing cells.
DNA REPAIR AND REPLICATION. The scientific activity has been also focused on the role of p21CDKN1A (p21) protein in the mechanism of repair induced by UV, in replication and in the biological activity of some natural and synthetic compounds.
The antiproliferative effect of beta-carotene has been detected in human fibroblasts. This effect is p21 dependent with the inhibition of the CDK4/cyclin D4 complex and the hypophoforilation of Rb protein. The antiproliferative and pro-apoptotic effects of two anthocyanins (delphinidin and cyanidine) present in blackcurrant were studied. It has been demonstrated the antiproliferative effects of cyanidin and delphinidine in normal human fibroblast and the pro-apoptotic effect of delphinidine in tumour cell lines. The apoptosis was activated through a mitochondrial pathway.
The interaction of Proliferating Cell Nuclear Antigen (PCNA) with p21, a kinase inhibitor has been detected in nucleotide excision repair (NER). Using a p21-GFP fusion protein it has been recently demonstrated that p21 colocalizes with PCNA at DNA replication sites, and that p21 does not interfere with PCNA binding to DNA replication sites, but it inhibits the subsequent association between PCNA and DNA polymerase delta inducing cell cycle arrest in G1/S phase.
It has been demonstrated that p21 is rapidly recruited to UV-induced DNA-damage sites, where it colocalises with PCNA and PCNA-interacting proteins, such as DNA polymerase delta, XPG and CAF-1. The presence of p21, however, does not interfere with DNA repair process. Recently, the results indicate that p21 is required during DNA repair to regulate histone acetyltransferase (HAT) p300 activity by disrupting its interaction with PCNA. The involvement of p21, in controlling the temporary entry from cell cycle (quiescence) was also studied. Possible effects of p21 on the composition and/or activity of PCNA complexes on DNA repair remain to be clarified by future studies. A the moment, her attention is focused on the protein that binds to damaged DNA (DDB2), which, combined with DDB1 in the complex DDB, exerts a key role in the recognition of DNA damage induced by UV in the Global Genome Repair (GGR-NER). Modifying a conserved region of DDB2, she has found an interaction site for PCNA. Presently, she is investigating the function of this interaction that seems to be necessary for the correct NER process execution and cell cycle progression.
In addition, she is studying in the biological activity of new compounds that have a fluoroquinolone-based structure for their use as photodynamic therapy, with the main goal to investigate their mechanisms of action (cell localization, DNA adducts formation, DNA repair processes activation, apoptosis).
DNA REPAIR AND REPLICATION. The scientific activity has been also focused on the role of p21CDKN1A (p21) protein in the mechanism of repair induced by UV, in replication and in the biological activity of some natural and synthetic compounds.
The antiproliferative effect of beta-carotene has been detected in human fibroblasts. This effect is p21 dependent with the inhibition of the CDK4/cyclin D4 complex and the hypophoforilation of Rb protein. The antiproliferative and pro-apoptotic effects of two anthocyanins (delphinidin and cyanidine) present in blackcurrant were studied. It has been demonstrated the antiproliferative effects of cyanidin and delphinidine in normal human fibroblast and the pro-apoptotic effect of delphinidine in tumour cell lines. The apoptosis was activated through a mitochondrial pathway.
The interaction of Proliferating Cell Nuclear Antigen (PCNA) with p21, a kinase inhibitor has been detected in nucleotide excision repair (NER). Using a p21-GFP fusion protein it has been recently demonstrated that p21 colocalizes with PCNA at DNA replication sites, and that p21 does not interfere with PCNA binding to DNA replication sites, but it inhibits the subsequent association between PCNA and DNA polymerase delta inducing cell cycle arrest in G1/S phase.
It has been demonstrated that p21 is rapidly recruited to UV-induced DNA-damage sites, where it colocalises with PCNA and PCNA-interacting proteins, such as DNA polymerase delta, XPG and CAF-1. The presence of p21, however, does not interfere with DNA repair process. Recently, the results indicate that p21 is required during DNA repair to regulate histone acetyltransferase (HAT) p300 activity by disrupting its interaction with PCNA. The involvement of p21, in controlling the temporary entry from cell cycle (quiescence) was also studied. Possible effects of p21 on the composition and/or activity of PCNA complexes on DNA repair remain to be clarified by future studies. A the moment, her attention is focused on the protein that binds to damaged DNA (DDB2), which, combined with DDB1 in the complex DDB, exerts a key role in the recognition of DNA damage induced by UV in the Global Genome Repair (GGR-NER). Modifying a conserved region of DDB2, she has found an interaction site for PCNA. Presently, she is investigating the function of this interaction that seems to be necessary for the correct NER process execution and cell cycle progression.
In addition, she is studying in the biological activity of new compounds that have a fluoroquinolone-based structure for their use as photodynamic therapy, with the main goal to investigate their mechanisms of action (cell localization, DNA adducts formation, DNA repair processes activation, apoptosis).
1) L.A. STIVALA, M. SAVIO, F. CARAFOLI, P. PERUCCA, L. BIANCHI, G. MAGA, L. FORTI, U.M. PAGNONI, A. ALBINI, E. PROSPERI, V. VANNINI.
Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol.
The Journal of Biological Chemistry, 276: 22586-22594, 2001.
2) O. CAZZALINI, P. PERUCCA, F. RIVA, L.A. STIVALA, L. BIANCHI, V. VANNINI, B. DUCOMMUN, E. PROSPERI.
p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but inhibits subsequent binding of DNA polymerase δ at the G1/S phase transition.
Cell Cycle, 2: 596-603, 2003
3) M.C. LAZZE’, M. SAVIO, R. PIZZALA, O. CAZZALINI, P. PERUCCA, A.I. SCOVASSI, L.A. STIVALA, L. BIANCHI
Anthocyanins induce cell cycle perturbations and apoptosis in different human cell lines. Carcinogenesis, 25(8): 1427-33, 2004
4) O. CAZZALINI*, P. PERUCCA *, F. VALSECCHI, L.A. STIVALA, L. BIANCHI, V. VANNINI, E. PROSPERI
Intracellular localization of the cyclin-dependent kinase inhibitor p21(CDKN1A)-GFP fusion protein during cell cycle arrest.
Histochem Cell Biol., 121(5): 377-81, 2004
*contributed equally to this work.
5) M.C. LAZZE’, R. PIZZALA, P. PERUCCA, O. CAZZALINI, M. SAVIO, L. FORTI, V. VANNINI, L. BIANCHI
Anthocyanidins decrease endothelin-1 production and increase endothelial nitric oxide synthase in human endothelial cells.
Mol Nutr Food Res., 50(1): 44-51, 2005
6) P. PERUCCA, O. CAZZALINI, O. MORTUSEWICZ, D. NECCHI, M. SAVIO, T. NARDO, L.A. STIVALA, H. LEONHARDT, M.C. CARDOSO, E. PROSPERI.
Spatio-temporal dynamics of p21CDKN1A protein recruitment to DNA damage sites and interaction with proliferating cell nuclear antigen.
Journal of Cell Science, 119 (8):1517-27, 2006
7) M. SAVIO, M. CERRI, O. CAZZALINI, P. PERUCCA, L.A. STIVALA, P. PICHIERRI, A.P. FRANCHITTO, L. MEIJER, E. PROSPERI.
Replication-dependent S-phase checkpoint triggered by Roscovitine induces an uncoupling of DNA replication proteins.
Cell Cycle, 5 (18): 2153-9, 2006
8) O. CAZZALINI, P. PERUCCA, M. SAVIO, D. NECCHI, L. BIANCHI L.A. STIVALA, B. DUCOMMUN, A.I. SCOVASSI, E. PROSPERI.
Interaction of p21CDKN1A with PCNA regulates the histone acetyltransferase activity of p300 in nucleotide excision repair.
Nucleic Acids Research, 36: 1713-1722, 2008
9) P. PERUCCA, O. CAZZALINI, M. MADINE, M. SAVIO, R.A. LASKEY, V. VANNINI, E. PROSPERI, L.A. STIVALA.
Loss of p21(CDKN1A) impairs entry to quiescence and activates a DNA damage response in normal fibroblasts induced to quiescence.
Cell Cycle, 8 (1): 105-14, 2009
10) M. SAVIO, T. COPPA, O. CAZZALINI, P. PERUCCA, D. NECCHI, T. NARDO, L.A. STIVALA, E. PROSPERI
Degradation of p21CDKN1A after DNA damage is independent of type of lesion, and is not required for DNA repair.
DNA Repair (Amst), 8(7):778-85, 2009.
11) M. SAVIO, T. COPPA, L. BIANCHI, V. VANNINI, G. MAGA, L. FORTI, O. CAZZALINI, M.C. LAZZÈ, P. PERUCCA, E. PROSPERI, L.A. STIVALA.
The resveratrol analogue 4,4'-dihydroxy-trans-stilbene inhibits cell proliferation with higher efficiency but different mechanism from resveratrol.
Int J Biochem Cell Biol., 41(12):2493-502, 2009.
12) O. CAZZALINI, F. DONÀ, M. SAVIO, M. TILLHON, C. MACCARIO, P. PERUCCA, L.A. STIVALA, A.I. SCOVASSI, E. PROSPERI.
p21CDKN1A participates in base excision repair by regulating the activity of poly(ADP-ribose) polymerase-1.
DNA Repair (Amst), 9(6):627-35, 2010.
13) T. COPPA, M.C. LAZZÈ, O. CAZZALINI, P. PERUCCA, R. PIZZALA, L. BIANCHI, L.A. STIVALA, L. FORTI, C. MACCARIO, V. VANNINI, M. SAVIO.
Structure-Activity Relationship of Resveratrol and Its Analogue 4,4'-Dihydroxy-Trans-Stilbene Toward the Endothelin Axis in Human Endothelial Cells.
J Med Food, 14(10): 1173-80, 2011
14) CAZZALINI O*, PERUCCA P*, MOCCHI R, SOMMATIS S, PROSPERI E, STIVALA LA.
DDB2 association with PCNA is required for its degradation after UV-induced DNA damage.
Cell Cycle, 13(2):240-8, 2014
*contributed equally to this work
15) PERUCCA P, SAVIO M., CAZZALINI O, MOCCHI R, C. MACCARIO, SOMMATIS S, FERRARO D., PIZZALA R., PRETALI L., FASANI E., ALBINI A., STIVALA LA
Structure-activity relationship and role of oxygen in the potential antitumour activity of fluoroquinolones in human epithelial cancer cells.
Journal of Photochemistry and Photobiology B: Biology 140: 57–68, 2014
16) PERUCCA P, SOMMATIS S, MOCCHI R, PROSPERI E, STIVALA LA. CAZZALINI O.
A DDB2 mutant protein unable to interact with PCNA promotes cell cycle progression of human transformed embryonic kidney cells.
Cell Cycle, 14 (24): 3920-8, 2015
17) VETRO A, SAVASTA S, ROSSI RAUCCI A, CERQUA C, SARTORI G, LIMONGELLI I, FORLINO A, MARUELLI S, PERUCCA P, VERGANI D, MAZZINI G, MATTEVI A, STIVALA LA, SALVIATI L, ZUFFARDI O
MCM5: a new actor in the link between DNA replication and Meier-Gorlin syndrome.
Eur J Hum Genet. 25(5): 646-650, 2017 doi: 10.1038/ejhg.2017.5.
Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol.
The Journal of Biological Chemistry, 276: 22586-22594, 2001.
2) O. CAZZALINI, P. PERUCCA, F. RIVA, L.A. STIVALA, L. BIANCHI, V. VANNINI, B. DUCOMMUN, E. PROSPERI.
p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but inhibits subsequent binding of DNA polymerase δ at the G1/S phase transition.
Cell Cycle, 2: 596-603, 2003
3) M.C. LAZZE’, M. SAVIO, R. PIZZALA, O. CAZZALINI, P. PERUCCA, A.I. SCOVASSI, L.A. STIVALA, L. BIANCHI
Anthocyanins induce cell cycle perturbations and apoptosis in different human cell lines. Carcinogenesis, 25(8): 1427-33, 2004
4) O. CAZZALINI*, P. PERUCCA *, F. VALSECCHI, L.A. STIVALA, L. BIANCHI, V. VANNINI, E. PROSPERI
Intracellular localization of the cyclin-dependent kinase inhibitor p21(CDKN1A)-GFP fusion protein during cell cycle arrest.
Histochem Cell Biol., 121(5): 377-81, 2004
*contributed equally to this work.
5) M.C. LAZZE’, R. PIZZALA, P. PERUCCA, O. CAZZALINI, M. SAVIO, L. FORTI, V. VANNINI, L. BIANCHI
Anthocyanidins decrease endothelin-1 production and increase endothelial nitric oxide synthase in human endothelial cells.
Mol Nutr Food Res., 50(1): 44-51, 2005
6) P. PERUCCA, O. CAZZALINI, O. MORTUSEWICZ, D. NECCHI, M. SAVIO, T. NARDO, L.A. STIVALA, H. LEONHARDT, M.C. CARDOSO, E. PROSPERI.
Spatio-temporal dynamics of p21CDKN1A protein recruitment to DNA damage sites and interaction with proliferating cell nuclear antigen.
Journal of Cell Science, 119 (8):1517-27, 2006
7) M. SAVIO, M. CERRI, O. CAZZALINI, P. PERUCCA, L.A. STIVALA, P. PICHIERRI, A.P. FRANCHITTO, L. MEIJER, E. PROSPERI.
Replication-dependent S-phase checkpoint triggered by Roscovitine induces an uncoupling of DNA replication proteins.
Cell Cycle, 5 (18): 2153-9, 2006
8) O. CAZZALINI, P. PERUCCA, M. SAVIO, D. NECCHI, L. BIANCHI L.A. STIVALA, B. DUCOMMUN, A.I. SCOVASSI, E. PROSPERI.
Interaction of p21CDKN1A with PCNA regulates the histone acetyltransferase activity of p300 in nucleotide excision repair.
Nucleic Acids Research, 36: 1713-1722, 2008
9) P. PERUCCA, O. CAZZALINI, M. MADINE, M. SAVIO, R.A. LASKEY, V. VANNINI, E. PROSPERI, L.A. STIVALA.
Loss of p21(CDKN1A) impairs entry to quiescence and activates a DNA damage response in normal fibroblasts induced to quiescence.
Cell Cycle, 8 (1): 105-14, 2009
10) M. SAVIO, T. COPPA, O. CAZZALINI, P. PERUCCA, D. NECCHI, T. NARDO, L.A. STIVALA, E. PROSPERI
Degradation of p21CDKN1A after DNA damage is independent of type of lesion, and is not required for DNA repair.
DNA Repair (Amst), 8(7):778-85, 2009.
11) M. SAVIO, T. COPPA, L. BIANCHI, V. VANNINI, G. MAGA, L. FORTI, O. CAZZALINI, M.C. LAZZÈ, P. PERUCCA, E. PROSPERI, L.A. STIVALA.
The resveratrol analogue 4,4'-dihydroxy-trans-stilbene inhibits cell proliferation with higher efficiency but different mechanism from resveratrol.
Int J Biochem Cell Biol., 41(12):2493-502, 2009.
12) O. CAZZALINI, F. DONÀ, M. SAVIO, M. TILLHON, C. MACCARIO, P. PERUCCA, L.A. STIVALA, A.I. SCOVASSI, E. PROSPERI.
p21CDKN1A participates in base excision repair by regulating the activity of poly(ADP-ribose) polymerase-1.
DNA Repair (Amst), 9(6):627-35, 2010.
13) T. COPPA, M.C. LAZZÈ, O. CAZZALINI, P. PERUCCA, R. PIZZALA, L. BIANCHI, L.A. STIVALA, L. FORTI, C. MACCARIO, V. VANNINI, M. SAVIO.
Structure-Activity Relationship of Resveratrol and Its Analogue 4,4'-Dihydroxy-Trans-Stilbene Toward the Endothelin Axis in Human Endothelial Cells.
J Med Food, 14(10): 1173-80, 2011
14) CAZZALINI O*, PERUCCA P*, MOCCHI R, SOMMATIS S, PROSPERI E, STIVALA LA.
DDB2 association with PCNA is required for its degradation after UV-induced DNA damage.
Cell Cycle, 13(2):240-8, 2014
*contributed equally to this work
15) PERUCCA P, SAVIO M., CAZZALINI O, MOCCHI R, C. MACCARIO, SOMMATIS S, FERRARO D., PIZZALA R., PRETALI L., FASANI E., ALBINI A., STIVALA LA
Structure-activity relationship and role of oxygen in the potential antitumour activity of fluoroquinolones in human epithelial cancer cells.
Journal of Photochemistry and Photobiology B: Biology 140: 57–68, 2014
16) PERUCCA P, SOMMATIS S, MOCCHI R, PROSPERI E, STIVALA LA. CAZZALINI O.
A DDB2 mutant protein unable to interact with PCNA promotes cell cycle progression of human transformed embryonic kidney cells.
Cell Cycle, 14 (24): 3920-8, 2015
17) VETRO A, SAVASTA S, ROSSI RAUCCI A, CERQUA C, SARTORI G, LIMONGELLI I, FORLINO A, MARUELLI S, PERUCCA P, VERGANI D, MAZZINI G, MATTEVI A, STIVALA LA, SALVIATI L, ZUFFARDI O
MCM5: a new actor in the link between DNA replication and Meier-Gorlin syndrome.
Eur J Hum Genet. 25(5): 646-650, 2017 doi: 10.1038/ejhg.2017.5.
No projects are available to students for the current accademic year.