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.
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.
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