DNA replication and anticancer therapeutics

Prof Corrado Santocanale

Prof of Molecular Medicine, NCBES, NUI Galway, 2007

Project leader, Nerviano R&D Oncology discovery site (Pharmacia, Pfizer, Nerviano Medical Sciences), 2000

PhD (Mol & Cell Biol), University of Milan, Italy, 1993

BA (Biology), University of Milan, Italy, 1988
  • email: corrado.santocanale@nuigalway.ie
  • phone: +353 91 49 5174
  • post: National Centre for Biomedical Engineering Science, Orbsen Building, NUI Galway, University Rd, Galway, Ireland

Research Interests

  • Mechanisms of DNA replication
  • Mechanisms regulating Cdc7 kinase activity
  • Target identification and characterization for cancer treatment
  • Development of therapeutic strategies in haematological malignancies

Research Overview


Cover of Nature Chemical Biology featuring our work with Cdc7

DNA replication is one of the most critical processes for the faithful transmission of genetic information from mother to daughter cell. Defects in the replication machinery can lead to tumorigenesis, while uncontrolled entry into S-phase is one of the hallmarks of cancer. DNA replication is also the target mechanism for both established chemotherapeutic drugs and new compounds that are being investigated at clinical and preclinical levels as anticancer drugs.

Our lab is interested in studying the mechanisms that regulate DNA replication in human cancer cells with particular emphasis on the Cdc7 kinase. Cdc7 acts as a molecular switch for DNA synthesis and is also thought to participate in several other processes that regulate normal cell cycle progression and chromosome dynamics.

The identification of new substrates and the characterization of the physiological processes in which Cdc7 is involved, will be pivotal in understanding in what disease context Cdc7 inhibitors may be used, and in developing novel biomarkers, thus providing valuable information and tools for rationally driving patient selection and devising combination therapies in preclinical and clinical settings. In addition, these studies will impact on our basic understanding of genome duplication, providing key insights into its mechanistics and regulation.

Key Publications

  • Kliszczak AE, Rainey MD, Harhen B, Boisvert FM, Santocanale C, DNA mediated chromatin pull-down for the study of chromatin replication. Scientific Reports 1: 95 (2011)
  • Natoni A, Murillo LS, Kliszczak AE, Catherwood MA, Montagnoli A, Samali A, O'Dwyer M, Santocanale C, Mechanisms of action of a dual Cdc7/Cdk9 kinase inhibitor against quiescent and proliferating CLL cells. Mol Cancer Ther 10: 1624-1634 (2011)
  • Montagnoli A, Valsasina B, Croci V, Menichincheri M, Rainoldi S, Marchesi V, Tibolla M, Tenca P, Brotherton D, Albanese C, Patton V, Alzani R, Ciavolella A, Sola F, Molinari A, Volpi D, Avanzi N, Fiorentini F, Cattoni M, Healy S, Ballinari D, Pesenti E, Isacchi A, Moll J, Bensimon A, Vanotti E, Santocanale C, A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol 4: 357-365 (2008)
  • Tenca P, Brotherton D, Montagnoli A, Rainoldi S, Albanese C, Santocanale C, Cdc7 is an active kinase in human cancer cells undergoing replication stress. J Biol Chem 282: 208-215 (2007)
  • Montagnoli A, Tenca P, Sola F, Carpani D, Brotherton D, Albanese C, Santocanale C, Cdc7 inhibition reveals a p53-dependent replication checkpoint that is defective in cancer cells. Cancer Res 64: 7110-7116 (2004)

Selected Links