1. BRCA1 Breast Cancer 1, Early Onset Simple gene, or breast/ovarian cancer’s best friend? By:Courtney Abshier

2. What is Breast Cancer?  Number one cause of Cancer  Hereditary vs. Sporadic  BRCA1 and BRCA2 California Pacific Medical Center. www.cpmc.org www.cpmc.org www.breastcancer.org

3. BRCA1 Mutations and Cancer  Hereditary  80% Chance of Breast Cancer  40% Chance of Ovarian Cancer  Kudson’s two hit model  Accounts for only 3-5% of breast cancer California Pacific Medical Center. www.cpmc.org www.cpmc.org www.breastcancer.org

4. Who found it and what is it?  Found in 1991 by Marie-Claire King.  Located on the 17 th Chromosome.  Tumor Suppressor Gene Genetics Home Reference. Ghr.nlm.nih.gov/dynamic Images/chromap/brca1.jpeg

5. What is its normal function for the cell?  Repair of Double Stranded Breaks in DNA  Homologous Recombination vs. Non- Homologous End Joining  BRCA1 and Homologous Recombination Powell, S and Kachnic, L. (2003) Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and cellular response to ionizing radiation. Oncogene 22, 5784-5791.

6. Process of Homologous Recombination http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/genetic-analysis/recombination/ds-break-rec.gif www.whfreeman.com/lodish

7. Functional Groups and other activities of the Protein N-terminal Ring Finger Domain C-terminal DNA binding/BRCT domains Nardo, S. and Foulkes, W.(2004) BRCA1 and BRCA2: Nardo, S. and Foulkes, W.(2004) BRCA1 and BRCA2: 1994 and Beyond.Nature Reviews 4, 665-676. 1994 and Beyond.Nature Reviews 4, 665-676.

8. How and Where do BRCA1 mutations arise?  Insertions, Deletions and Nonsense mutations  Mutations at all parts  Increase of mutations on exon 11 Brodie S. and Deng C. (2001) BrCA1-associated tumorigenesis: what have we learned from knockout mice? Trends in Genetics 17, 18-22. we learned from knockout mice? Trends in Genetics 17, 18-22.

9. Knockout Mice  Null mice died early during embryonic development  BRCA1 deficient cells repaired DNA through NHEJ Brodie S. and Deng C. (2001) BrCA1-associated tumorigenesis: what have welearned from knockout mice? Trends in Genetics 17, 18-22. welearned from knockout mice? Trends in Genetics 17, 18-22.

10. How does this protein then contribute to cancer?  Involvement in DNA repair  Involvement in cell cycle checkpoints  Accumulation of cells with mutated DNA Nardo, S. and Foulkes, W.(2004) BRCA1 and BRCA2 1994 and Beyond.Nature Reviews 4, 665-676. 1994 and Beyond.Nature Reviews 4, 665-676.

11. If BRCA1 plays such a central role in development, why does it only cause breast and ovarian cancer?  Oestrogen release in breast and ovarian area  Prosurvival signals from surrounding cells Nardo, S. and Foulkes, W.(2004) BRCA1 and BRCA2: 1994 and Beyond.Nature Reviews 4, 665-676.