Prof Corrado Santocanale

Professor of Molecular Medicine
SFI Principal Investigator

Research interests

  • Mechanisms of genome replication: function and regulation of Cdc7 kinase
  • Cancer therapeutics

Research overview

The process of DNA replication is the biggest threat for genome stability in all proliferating cells. Cancer cells in particular are subjected to replication stress after activation of proto-oncogenes into their oncogenic forms or due to deficiency in specific factors required for genome duplication. Thus aberrant DNA replication contributes to initiating and maintaining the cancerous state, while drugs targeting DNA synthesis have potent antitumor activity and are key component of current and novel chemotherapeutic regimens.
Our laboratory is studying the mechanisms that regulate genome replication in human cells with particular emphasis on the Cell Division Cycle 7 kinase (CDC7). 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.

We have adopted chemical biology and gene editing approaches to characterize the molecular processes in which CDC7 is involved and to detect new substrates of the kinase. We are performing genome-wide CRISPR/Cas9 screens to identify genes that alter the cellular responses and make cells more sensitive or resistant to CDC7 inhibition.
This information will be pivotal in understanding in what disease context emerging CDC7 inhibitors may be used for the cancer treatment, 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.
We are also interested in understanding the roles of the Ubiquitin Specific Protease 9X (USP9X) which in context dependent manner can act as either an oncogene or a tumour suppressor. We have recently discovered that USP9X contributes to genome stability by promoting forks stability and efficient DNA repair, but by different mechanisms.

In the past we have established a technique for the purification and characterization of proteins associated to newly replicated DNA that we called DNA mediated chromatin pull down (Dm-ChP). This technique has been particularly useful in understanding which proteins acts at forks during unperturbed replication, upon replication stress and in different genetic backgrounds.


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

Selected publications

  • O'Dea R, and Santocanale C. Non-canonical regulation of homologous recombination DNA repair by the USP9X deubiquitylase. Journal of Cell Science (2020) 133: jcs233437 doi: 10.1242/jcs.233437 PMID: 31964704
  • Rainey MD, Quachthithu H, Gaboriau D, Santocanale C. DNA Replication Dynamics and Cellular Responses to ATP Competitive CDC7 Kinase Inhibitors. ACS Chem Biol. (2017) Jul 21;12(7):1893-1902. PMID: 28560864.
  • Wu KZ, Wang GN, Fitzgerald J, Quachthithu H, Rainey MD, Cattaneo A, Bachi A, Santocanale C. DDK dependent regulation of TOP2A at centromeres revealed by a chemical genetics approach. Nucleic Acids Res. (2016) Oct 14;44(18):8786-8798. PMID: 27407105.
  • Kliszczak AE, Rainey MD, Harhen B, Boisvert FM, Santocanale C. DNA mediated chromatin pull-down for the study of chromatin replication. Sci Rep. (2011);1:95. doi: 10.1038/srep00095. PMID: 22355613.
  • 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.