The Role of MYBL2 in DNA damage response to etoposide in mouse embryonic stem cells (ESCs) (360G-Wellcome-207318_Z_17_Z)

Embryonic Stem cells (ESC) share common characteristics with cancer cells such as immortality and the ability to bypass the normal cell cycle checkpoints somatic cells have to pass through. This allows both cells to continuously proliferate without changing their cellular features. These similarities shared between both ESCs and cancer cells may relate to common patterns and mechanisms of regulating gene expression. In fact, as demonstrated by Yamanaka fully differentiated fibroblast could reverse their state of differentiation and be induced towards an embryonic stem cell-like state (induced-pluripotent stem cells (iPSCs)) by introducing four transcription factors expressed in a pluripotency state. These observations highlighted the importance of transcriptional factors in determining cell fate and their possible role in the induction of cancer. In this project, I will be working with mouse ESCs and will be looking at the role of MYBL2, a transcription factor highly expressed in ESC and iPSC, which is involved in cell proliferation and maturation, and try to better understand its role in the maintenance of genome integrity. I will be exploring how low levels of this gene affect the cell response to topoisomerase II inhibitor etoposide, a therapy currently used in to treat cancer.