BIOL 401 Lecture Notes - Lecture 2: P53, Germline Mutation, Direct-Sequence Spread Spectrum
15 Jul 2016
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Document Summary
Brca1 or 2 = genomic instability due to defective double stranded break (dsb) repair. Mitosis checkpoint necessary to facilitate propagation of cells within genomic mutation. Guardian of genome aka p53 is key factor in cell-response to dna damage. P53 loss may aid brac1- and brca2 tumor development. Mouse studies show brca1-/- and brca2-/- as embryonic lethal p53 dependent up- regulation of p21^wafl. Trp53 knockout in brca1-/- and brca2 -/- partially rescue lethality to later stage in development. Mouse mammary tumors development in brca1+2 knowckout mice accelerated in trp53 knowckout background. Homozygous brca loss induce cell lethality via activating p53-dependent checkpoint impairment of this checkpoint by p53 loss alleviates cell-lethal effects of brca loss. Breast tumors from brca carriers increase freq of tp53 mutations. Usually scored indirectly by immunohistochemical detection (detects fraction tp53 mutations) of p53^ihc with dominant-(-) mutant p53 protein. Cells that stain (-) for p53 have wildtype p53 or tp53 mutations.
