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Embryonic stem cells (ESC) have an unlimited proliferation capacity, and are pluripotent cells since they preserved the potential to differentiate into all cell types of the adult organism [1–3]. Adult tissues and organs of higher vertebrates are mostly constituted of fully differentiated and specialized cells forming the tridimensional layout and enabling the biological functions of those tissues/organs, and a rare population of specific stem cells with restricted ability to differentiate into the mature cell types constituting the tissues/organs where they reside [4].

Depending on the nature and/or abundance of this damage different DNA repair pathways are involved, that together, form an extremely complex, interacting defense platform against genotoxic damage (summarized in Fig. 3). The DDR is a signal transduction pathway that is primarily mediated by proteins of the phosphatidylinositol 3-kinase-like protein kinases (PI3KKs) family many of which have been described in the repair of DSBs including, ATM, ATR and DNA-PK. In addition to these, there are also the poly(ADP) ribose polymerase (PARP) family.

3 A simplified schematic of the DNA-damage response. This figure indicates an overview of the key protein kinases and signalling intermediates within eukaryotic cells that are activated following the detection of a double strand break and the various cellular choices that they dictate, principally via the tumour suppressor and transcription factor p53 3 Apoptosis 37 enter terminal differentiation via senescence (permanent cell cycle arrest) or to temporarily induce cell cycle arrest allowing DNA repair to occur.

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