On the Cover: The p53 tumor suppressor protein is a critical guardian against cellular carcinogenesis and is a common mutation in many human cancers. It has been best characterized as a transcriptional transactivator that mediated cell cycle checkpoint control, DNA repair and/or cell death; however, its subcelluar locale and role in the early signaling following DNA damage remains poorly understood. Using whole cell targeted subnuclear irradiation, Al Rashid et al. have studied the biology of DNA damage-induced p53 phosphoforms within primary fibroblast. The top panel of eight images represent single confocal sections and three-dimensional rendered images (reconstructed from stacked confocal sections) which demonstrates that a subpool of phosphorylated p53^Ser15 is recruited to nuclear DNA-damage foci in γ-H2AX- and DNA-PKcs-positive regions at 1-3 hours following 1-2 Gy of irradiation. p53 proteins that are mutated at the Serine 15 residue are defective in foci formation and p21^WAF induction. The bottom panel depicts a model tha is proposed for the interaction between p53^Ser15 phosphoforms with DNS damage sensing/repair and signaling complexes within damaged chromatin to mediate cell cycle checkpoint control. Mutant p53 proteins incapable of similar phosphorylation could then drive gentic instability due to the inapporiate sensing of the extent and type of DNA damage. For details, see the article by Al Rashid et al. on page 10810 of this issue.

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