Strict regulation of DNA replication is an important procedure since cases of its dysfunction lead to development of replication stress, a frequent source of genomic instability. Replication stress-induced genomic instability has been widely associated with tumorigenesis and is lately considered to affect the innate immune system activation.
The replication licensing factor Cdt1 and its inhibitor Geminin are key regulators of DNA replication. Geminin binds to Cdt1 preventing relicensing of replication during the same cell cycle. According to previous studies of our research group, changes in expression levels of these proteins cause re-replication and are linked to signs of DNA damage contributing to the development of murine lung and colon carcinogenesis. We aim to elucidate the mechanism activated in inflammatory responses during genomic instability induced by the deregulation of Geminin and Cdt1 expression levels. One of our long-term goals is to provide insight on how inflammation determines the cancer progression, as well as to reveal molecular targets for anticancer therapy.
