Grant: Project Grant

Mobile genetic elements are regions of DNA that copy and paste themselves into a genome. More than half of the human genome is full of repetitive elements and movement of these elements can result in cancers as well as other disorders. The elements that move in the human genome are called retrotransposons. We use the budding yeast Saccharomyces cerevisiae (S. cerevisiae) and the Ty1 retrotransposon, which is present in 32 copies in the yeast genome, as a model system. The yeast Ty1 retrotransposon is similar in structure and life cycle to retroviruses such as the human immunodeficiency virus (HIV-1), which results in acquired immunodeficiency syndrome (AIDS). Studies of the Ty1 retrotransposon have already been important for elucidating the fundamental mechanisms of how retrotransposons/retroviruses replicate and enter the genome. In this research proposal, we will study the precise mechanism of how the Ty1 retrotransposon is pasted into a specific region of the genome. The highly conserved Ty1 integrase protein is necessary for pasting the retrotransposon into the genome but needs the help of host cellular proteins to accomplish genome entry. We will uncover which host proteins interact with Ty1 integrase and how this interaction results in targeting to a region of the genome. Because Ty1 integrase is conserved with retroviral integrases, and many yeast proteins are conserved with mammalian proteins, the knowledge we gain from our research can be applied to human cells and ultimately health care. Our fundamental research using a model organism is critical for understanding how disruptions can occur in the human genome.