Natasha Adlakha Bio445

Discovery in Breast CancerReverse Genetics

BReast CAncer Gene 2 -1995Chromosome 13Tumor suppressor gene

Penetrance Familial, sporadic –different “2 hit”

www.cellsignal.com/products/9012.html

Normal Functions•Aids in Homologous Recombination

Pellegrini et al 2004

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

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

Future ResearchTissue specificity – why breast? Gender bias Humanized mouse modelsSpecific genotype-phenotype correlations Paradox—secondary tumor suppressor gene

mutations

www.humurine.com/services.php