The regulation of cell division is crucial for the propagation of multicellular organisms and aberrations in proliferation are at the origin of cancer. We and others have recently discovered a novel pathway that is mediated by 53BP1, USP28 and p53 and monitors the duration of mitosis in the mouse in vivo and in cell lines in vitro. This “mitotic surveillance pathway” is activated upon prolonging mitosis through centrosome loss of function or mitotic drugs, and is largely independent of the well-studied spindle assembly checkpoint (SAC), DNA damage or aneuploidy. We hypothesize that this pathway is a bone fidecheckpoint that operates as a “mitotic timer” that monitors cell division duration. Our aim is to dissect the mechanism of this novel cell cycle “checkpoint” from the sensors to the mediators using live-imaging, biochemical and genetic approaches in mouse embryonic stem cells (mESCs).
How aberrations in cell division lead to human diseases such as microcephaly and malignancies like cancer are still open questions. Our work has defined a new p53-dependent pathway that monitors centrosomes and mitosis and ensures that only cells with normal mitotic duration are propagated. Our long-term goal of dissecting this mitotic surveillance pathway is to find druggable targets to help cure microcephaly during development and prevent cancer cells from proliferation and expansion.