Amber Caracol

Department: Molecular and Cellular Biology
Year Entered: 2004
Prior Degrees: BS, University of Hawaii, 2004

acaracol@u.washington.edu

Research Interests:
Topoisomerase I (Topo I) is an enzyme that relaxes DNA supercoils. Topo I forms a covalent protein-DNA intermediate between a tyrosine on the enzyme and a phosphate on the DNA backbone. Topo I nicks the DNA, performs a controlled rotation and re-ligates the DNA ends before releasing from the DNA. Camptothecin (CPT), a naturally occurring alkyloid, is a drug that prevents the release of Topo I from DNA. Accumulation of Topo I-DNA complexes can lead to cell death if not repaired through formation of double-strand breaks (DSB) upon DNA replication. The CPT derivatives, irinotecan and topotecan, are commonly used in cancer chemotherapy. Many tumors contain inactivating mutations in genes for DNA repair factors and these tumors may respond well to chemotherapeutics that cause DNA damage. My recent experiments have focused on understanding the role of the MRE11 nuclease in repairing CPT-induced DNA damage and determining whether loss of MRE11 expression in tumors correlates with sensitivity to treatment with the CPT-derived chemotherapeutic, irinotecan.

Why Molecular Medicine?
The Molecular Medicine Certificate Program has provided me with an opportunity to relate my basic science research of understanding the cellular functions of MRE11 to its potential applications in the clinic.