Analysis of the DNA Damage Signaling Network Important for Prevention of Breast Cancer
Final rept. 15 May 2001-14 May 2004
BAYLOR COLL OF MEDICINE HOUSTON TX
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Women with germilne mutations in the breast and ovarian cancer gene 1 Brcal have an approximately 50 lifetime risk of developing ovarian cancer and almost 90 chance of breast cancer. Brcal mutations account for a significant percentage of all breast cancer cases. It appears that the main role for the Brcal protein in cells is to prevent the accumulation of mutations in key growth regulatory genes in response to DNA damage. BRCAl is phosphorylated in response to DNA damage by an elaborate surveillance mechanism, called a checkpoint that detects DNA damage and prevents the accumulation of mutation. We are investigating the role these phosphorylation events play in the regulation of BRCAl. We have napped phosphorylation sites and will mutate them to determine their function. We are also planning to investigate the mechanism through which the BRCAl protein localizes to sites of DNA damage within cells.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research