Cells SB 223412 expressing S1333A-ATR have elevated basal phosphorylation levels of ATR substrates but no noticeable checkpoint or replication defects in cultured cells. Thus, cells can tolerate elevated basal ATR kinase activity. The small decrease in ATR activity caused by the S1333D mutation is enough to cause modest defects in some ATR checkpoint functions. S1333 is not in a region of ATR previously known to be involved in regulation of the kinase. Future high-resolution Talampanel structural studies will aid in understanding why this region is important to regulate ATR activity levels. The accumulation of green fluorescent protein in cells is widely used as a molecular tag that can be readily visualized under ultraviolet light illumination. Many different GFP-transgenic animals have been generated and utilized for tracking cells in organ and cell transplantation studies. GFP can show weak immunogenicity and/or cell toxicity that can potentially alter experimental results. Gambotto et al. showed that GFP could generate an antigenic epitope that binds to H2-Kd molecules in BALB/c mice, while Inoue and colleagues generated the GFP-Tg Lewis rat and reported that transplanted skin grafts from these rats to wild-type Lewis rats lost viability after about a week, suggesting immunological rejection. Nevertheless, isolated cells from GFP-Tg rats were observed long after cell transplantation into immune-privileged sites such as the central nervous system and joints. In addition, liver harvested from a GFP-Tg Lewis rat survived long term in a wild-type Lewis rat without the use of an immunosuppressant. These experimental findings imply that GFP is weakly immunogenic, but that organs or cells expressing GFP can survive at sites where there is a weaker immunological reaction. In general, transplanted allogeneic hepatocytes are eliminated within a few days without the use of an immunosuppressant. Nevertheless, studies with rat models suggest that GFP is minimally immunogenic when GFP-positive hepatocytes or stem/progenitor cells are transplanted into syngeneic liver. Oertel and colleagues transplanted hepatocytes transfected with the GFP gene into retrorsine-pretreated wild-type syngeneic rat liver. They demonstrated continuous GFP expression, driven by the liver-specific albumin enhancer/promoter, in transplanted hepatocytes up to four months after transplantation. Other studies showed repopulation of injured liver tissue by transplanted syngeneic stem/progenitor cells expressing GFP. Therefore, we expected to see long-term survival of GFP-positive hepatocytes after transplantation into a wild-type Lewis rat liver. In a pilot study, we did not observe proliferation of GFP-positive hepatocytes at six weeks after transplantation of a syngeneic liver specimen.