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Ku70, Ku80, and DNA-PKcs are subunits of the DNA-dependent protein kinase (DNA-PK), an enzyme implicated in DNA double-stranded break repair and V(D)J recombination. Our Ku70-deficient mice were about 50% the size of control littermates, and their fibroblasts were ionizing radiation sensitive and displayed premature senescence associated with the(More)
A common V(D)J recombinase that recognizes a conserved recombination signal sequence (RSS) mediates the assembly of immunoglobulin (Ig) and T cell receptor (TCR) genes in B and T cell precursors. The rearrangement of particular Ig and TCR gene segments, however, is tightly regulated with respect to cell lineage and developmental stage. Using an in vitro(More)
Antigen receptor genes are assembled from their component gene segments by a highly regulated series of site-specific DNA recombination reactions known as V(D)J recombination. Proteins encoded by the RAG1 and RAG2 genes are responsible for the recognition and double-stranded cleavage of a highly conserved DNA sequence flanking all rearranging gene segments.(More)
Deletion of the TCRbeta transcriptional enhancer (Ebeta) results in nearly complete inhibition of V(D)J recombination at the TCRbeta locus and a block in alpha beta T cell development. This result, along with previous work from many laboratories, has led to the hypothesis that transcriptional enhancers affect V(D)J recombination by regulating the(More)
The p53 tumor suppressor is phosphorylated in response to various cellular stress signals, such as DNA damage, leading to its release from MDM2 and consequent stabilization and activation as a transcription factor. In human U2OS cells, treatment with adriamycin causes p53 to be phosphorylated on all six serine residues tested, leading to the dissociation of(More)
Wilms tumors are a heterogeneous class of tumors in which Wilms tumor suppressor-1 (WT1) and the p53 tumor suppressor may be variously inactivated by mutation, reduced in expression, or even overexpressed in the wild-type state. The downstream transcriptional targets of WT1 and p53 that are critical for mediating their roles in Wilms tumorigenesis are not(More)
The Wilms tumor suppressor WT1 has transcription-activating and -suppressing capabilities. WT1-responsive promoters have been described; however, in large part, it remains unclear which potential downstream genes are physiologically relevant and mediate the function of WT1 in tumorigenesis and development. To identify genes regulated by WT1 in vivo, we used(More)
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