New insights into cell cycle regulation and DNA damage response in embryonic stem cells.

Embryonic stem cells (ESCs) have unlimited proliferative potential, while retaining the ability to differentiate into descendants of all three embryonic layers. High proliferation rate of ESCs is accompanied by a shortening of the G(1) phase and the lack of G(1) checkpoint following DNA damage. The absence of G(1) arrest in ESCs after DNA damage is likely caused by a dysfunction of the p53-dependent p21Waf1 pathway that is a key event for the maintenance of pluripotency. There are controversial data on the functional status of p53, but it is well established that one of the key p53 target-p21Waf1-is expressed in ESCs at a very low level. Despite the lack of G(1) checkpoint, ESCs are capable to repair DNA defects; moreover the DNA damage response (DDR) signaling operates very effectively throughout the cell cycle. This review covers also the results obtained with the reprogramming of somatic cells into the induced pluripotent stem cells, for which have been shown that a partial dysfunction of the p53Waf1 pathway increases the frequency of generation of pluripotent cells. In summary, these results indicate that the G(1) checkpoint control and DDR are distinct from somatic cells and their status is tightly connected with maintaining of pluripotency and self-renewal.