Role of SRCAP and H.2AZ in Breast Cancer Cells

The fact that CSCs are able to escape anti-cancer drugs and cause post-chemotherapy relapse makes them very attractive as a therapeutical target. They have been identified in a variety of cancers, where they have the ability to self-renew and give rise to non-self-renewing cancer cells. In other words, they regain their cellular identity after each division, even though mitosis proposes a great challenge for the propagation of gene expression programs. This process can be facilitated by mitotic bookmarkers. The transcription factor complex YAP/TAZ-TEAD has been implicated as such. In addition, these proteins have been defined as oncogenes, drivers of tumorigenesis and able to promote self-renewal and chemoresistance in cancer stem cells. Therefore, I will focus on how the YAP/TAZ-TEAD complex influences CSC identity maintenance during mitosis and re-instates gene regulation at the mitosis-G1 transition. For this I will utilize sequencing applications to characterize the binding of YAP/TAZ/TEAD and the chromosomal landscape around their binding sites. Then I will perform loss of function studies with mitotic and mitotic exit specific degron systems, to finally investigate CSC self renewal in a 3D culture system.