Nikola Panayot Pavletich

Leader in using structural biology and biochemistry to analyze cellular processes that are perturbed in cancer. Studies of proteins regulating the DNA-damage responses, cell cycle, and ubiquitin system yielded structural and mechanistic insights into key events in carcinogenesis. Work addressed functions of key proteins that suppress or enhance tumorigenesis. Published first detailed structural studies of p53 tumor suppressor, a transcription factor that regulates DNA damage response and is the most frequently mutated gene in human cancer. Most recent contribution is the structure of mTOR, a protein kinase that controls cell growth and is frequently deregulated in cancer. Contributions in the cell cycle field include the mechanistic underpinnings of the on/off switches mediated by cyclin-dependent kinases and key aspects of mechanisms of action of specific ubiquitin ligases. Advanced understanding of DNA repair through analysis of the roles of tumor suppressor BRCA2 in homology-directed repair and elucidation of the structure of RecA recombinase bound to DNA, resolving many long-standing questions about the mechanism of homologous recombination.