natasha adlakha bio445. discovery in breast cancer reverse genetics breast cancer gene 2 -1995...
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Normal Functions Aids in Homologous Recombination Pellegrini et al 2004TRANSCRIPT
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Natasha Adlakha Bio445
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Discovery in Breast CancerReverse Genetics
BReast CAncer Gene 2 -1995Chromosome 13Tumor suppressor gene
Penetrance Familial, sporadic –different “2 hit”
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Normal Functions•Aids in Homologous Recombination
Pellegrini et al 2004
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Powell et al 2003
Key points•BRCA2, RAD51 arrive at damaged site•Complex formation • Quandary of BRC4•No BRCA2 protein leads to instability:
•Breaks and aberrations •Repair by non-homologous end joining (below)
Takeda et al 2001
Powell et al 2003
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Mice Knockout leads to..?-/- die early in developmentRole of p53 Limitations of mice –use Cre-lox Results BRCA-2 Paradox
http://www2.mrc-lmb.cam.ac.uk/groups/kjp/research.html
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Future ResearchTissue specificity – why breast? Gender bias Humanized mouse modelsSpecific genotype-phenotype correlations Paradox—secondary tumor suppressor gene
mutations
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