RIG: The Role of POT1 in Telomere Maintenance and Protection

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Telomeres are essential for chromosome stability because they provide protection to chromosome ends, which would otherwise be detected as DNA breaks, and they ensure their proper replication. The main hypothesis of this project is that POT1, the overhang binding protein at telomeres, regulates both telomerase-mediated telomere maintenance and telomere protection. A molecular genetic analysis of POT1 function will be carried out to elucidate how this regulation is achieved. To that end, the investigator will construct a conditional POT1 knockout in somatic cells, thereby providing a clean genetic system in which to study POT1 function. The strategy entails introducing LoxP recombination sites on either side of a POT1 exon in order to induce the POT1-null phenotype at will upon expression of Cre recombinase. This work will produce an experimental system tailored for the study of the short-term and long-term effects of POT1 loss, and for detecting any rescue of the cells by specific alleles or domains of POT1 and other candidate proteins. The project is well-suited to the training of students at the beginning of theirscientific careers. It will teach them the subtleties of molecular genetic analysisand the possible impact of specific pathways on cell viability. The student body at Hunter College is one of the most diverse in the nation, and is largely undergraduate. Undergraduates will have the opportunity to be directly involved in modern molecular biological research, while taking classes in cell biology, biochemistry and genetics.