Double minutes

Kaufman RJ, Brown PC, Schimke RT. Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes. Proc Natl AcadSci USA 1979 76 5669-5673. 

Lu et u/. screened a prefiltered set of 11000 compounds from the NCI database with a pharmacophore model based on the crystal structure of murine double minute 2 (MDM2) oncoprotein in complex with the p53 tumor suppressor and several non-peptide small inhibitors. The remaining compounds were docked, scored, and 67 compounds were selected for testing, ten of which were active in a competitive binding assay. Similarly, Yu et used a Catalyst HipHop model combined with the molecular shape of an experimental X-ray... 

Garcia-Echeverria, C., Chene, P., Blom-mers, M. J., and Furet, P. (2000) Discovery of potent antagonists of the interaction between hitman double minute 2 and tumor suppressor p53. J. Med. Chem. 43, 3205-3208. 

Liu G, Schwartz JA, Brooks SC (2000) Estrogen receptor protects p53 from deactivation by human double minute-2. Cancer Res, 60 1810-1814. 

Allen JG, Bourbeau MP, Wohlhieter GE et al (2009) Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2-tumor protein 53 protein-protein interaction. J Med Chem 52 7044—7053... 

Fakharzadeh SS, Rosenblum-Vos L, Murphy M et al (1993) Structure and organization of amplified DNA on double minutes containing the mdm2 oncogene. Genomics 15 283-290... 

Hardcastle IR, Liu J, Valeur E et al (2011) Isoindolinone inhibitors of the murine double minute 2 (MDM2)-p53 protein-protein interaction structure-activity studies leading to improved potency. J Med Chem 54 1233-1243... 

Ambrosini G, Sambol EB, Carvajal D et al (2007) Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1. Oncogene 26 3473-3481... 

Binder BR (2007) A novel application for murine double minute 2 antagonists the p53 tumor suppressor network also controls angiogenesis. Circ Res 100 13-14... 

Drakos E, Thomaides A, Medeiros LJ et al (2007) Inhibition of p53-murine double minute 2 interaction by Nutlin-3A stabilizes p53 and induces cell cycle arrest and apoptosis in Hodgkin lymphoma. Clin Cancer Res 13 3380-3387... 

Vitek, J.A. (1987) Similarity in dynamics of single and double minute chromosomes incidence and number of chromosomal aberrations during long-term treatment of a human cell line with methotrexate. Neoplasma 34, 6 665-670. 

Amplification of genes under selective conditions has been widely observed-for example, in development of pesticide-resistant forms of insects. Such amplified structures could arise either through recombination with unequal sister-chromatid exchange, schematized in Figure 25.41, or by a conservative transposition process. Later, homologous recombination within an amplified region can lead to excision of sequences containing one or more amplified sequences. In order to replicate autonomously, these excised sequences must have a centromere. Such elements probably represent the double-minute chromosomes. 

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