Natasha Adlakha Bio445

Discovery in Breast Cancer Reverse Genetics BReast CAncer Gene Chromosome 13 Tumor suppressor gene Penetrance Familial, sporadic –different “2 hit”

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 development Role of p53 Limitations of mice –use Cre-lox Results BRCA-2 Paradox lmb.cam.ac.uk/groups/kjp/researc h.html

Future Research Tissue specificity – why breast? Gender bias Humanized mouse models Specific genotype-phenotype correlations Paradox—secondary tumor suppressor gene mutations