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Individuals with Li-Fraumeni syndrome carry inherited mutations in the p53 tumor suppressor gene and are predisposed to tumor development. To examine the mechanistic nature of these p53 missense mutations, we generated mice harboring a G-to-A substitution at nucleotide 515 of p53 (p53+/515A) corresponding to the p53R175H hot spot mutation in human cancers.(More)
The ability of p53 to regulate transcription is crucial for tumor suppression and implies that inherited polymorphisms in functional p53-binding sites could influence cancer. Here, we identify a polymorphic p53 responsive element and demonstrate its influence on cancer risk using genome-wide data sets of cancer susceptibility loci, genetic variation, p53(More)
The Mystery of Minutes Lewis Carroll wrote about Alice, but he might just as well have been referring to Calvin Bridges. As a student in T.H. Morgan's lab, Bridges described some of the earliest Drosophila mutations, including so-called Minutes, in which heterozygotes exhibited small body size and developmental abnormalities in tissues undergoing rapid cell(More)
The tumour suppressor p53 is regulated primarily at the protein level. In normal tissues its levels are maintained at a very low level by the action of specific E3 ligases and the ubiquitin proteosome pathway. The mutant p53 protein contributes to transformation, metastasis and drug resistance. High levels of mutant p53 can be found in tumours and the(More)
Skin pigmentation disorders are among the most recognizable human diseases, strongly impacting both health and quality of life. Lentigines are small, hyper-pigmented skin macules, histologically containing increased numbers of melanocytes, typically producing Users may view, print, copy, and download text and data-mine the content in such documents, for the(More)
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