Ultraviolet-induced apoptosis in embryonic stem cells in vitro.

Embryonic stem (ES) cells, and the inner cell mass from which they are derived, are hypersensitive to DNA damage and appear to have specific cellular defense systems for DNA repair and the elimination of damaged cells. These mechanisms differ from somatic cells and are vital to minimize developmental defects that would potentially result from the continued proliferation and differentiation of abnormal cells into adult cell lineages. Although the DNA damage-induced signaling cascades activated in these cells are known to include p38 and c-Jun N-terminal protein kinase mitogen-activated protein kinase pathways and activation of a variety of transcription factors, including p53, nuclear factor-kappaB, and activator protein-1, the nature of the specific mechanisms unique to these cells remains to be elucidated. Here, we describe the use of homozygous knockout ES cells to investigate the role of Ets1 in the response to DNA damage in these cells. These studies demonstrate that Ets1 is required for optimal p53 function in this response and further demonstrate the potential for knockout ES cells to elucidate the role of specific genes in early embryonic cell responses.