Bazzi, Hisham - A 01

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 pharmacological treatments, and is largely independent of the well-studied spindle assembly checkpoint (SAC), DNA damage or aneuploidy. In this application, we hypothesize that this pathway is a bone fide checkpoint 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).

Our main aim is to decipher the mechanism of the mitotic surveillance pathway in mESCs and:

• Define the temporal steps of pathway activation from initiation to propagation
• Identify the sensors, mediators and executioners of the pathway
• Assess the functions of the players in the pathway

For more research information, please check Bazzi Lab.

• CDB, Umich, Ann Arbor, MI
• CECAD Cologne
• Cologne Graduate School of Aging Research (CGA)
• Stem Cell Network NRW