Prof Corrado Santocanale

Professor of Molecular Medicine
SFI Principal Investigator

Research interests

  • Mechanisms of genome duplication
  • Cancer therapeutics

Research overview

Genome duplication involves replicating DNA while maintaining the epigenetic information. These processes are critical for genome stability and for preserving cell-type identity. Uncontrolled entry into S-phase is one of the hallmarks of cancer, while defects in the replication machinery and in the proper maintenance of the epigenetic information can lead to tumorigenesis.

Our laboratory is interested in studying the mechanisms that regulate genome duplication 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.


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Visualization of ongoing DNA replication in human cells by dual labeling of nascent DNA and DNA fiber spreading technique.

We are combining proteomics, gene editing and chemical genetic approaches to identify new CDC7 substrates and interacting proteins. Their characterization will increase our knowledge of the physiological processes in which the kinase is involved and how its activity is regulated. This information will be pivotal in (1) understanding the best way emerging Cdc7 inhibitors may be used for cancer treatment and in the rational selection of patients, (2) in developing novel biomarkers and (3) in devising combination therapies in preclinical and clinical settings.

We also have established a technique for the purification and characterization of proteins associated with newly replicated DNA that we call DNA mediated chromatin pull down (Dm-ChP). This technique is rapidly rapidly advancing our understanding how DNA synthesis and chromatin assembly are coordinated.


For further information on the Santocanale lab or to meet the lab members click here

Selected publications

  • FitzGerald J, Murillo LS, O'Brien G, O'Connell E, O'Connor A, Wu K, Wang GN, Rainey MD, Natoni A, Healy S, O'Dwyer M, Santocanale C, A high through-put screen for small molecules modulating MCM2 phosphorylation identifies Ryuvidine as an inducer of the DNA damage response. PLoS One 9: e98891 (2014)
  • Rainey MD, Harhen B, Wang GN, Murphy PV, Santocanale C, Cdc7-dependent and -independent phosphorylation of Claspin in the induction of the DNA replication checkpoint. Cell Cycle 12: 1560-1568 (2013)
  • Kliszczak AE, Rainey MD, Harhen B, Boisvert FM, Santocanale C, DNA mediated chromatin pull-down for the study of chromatin replication. Sci Rep 1: 95 (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)