My lab uses a combination of biochemical and cell-based approaches to study factors involved in chromatin and DNA dynamics, with an emphasis on human disease models. We are particularly interested in ATP-driven motor proteins such as chromatin remodeling enzymes, helicases, and the recently discovered annealing helicases.
The study of the structure and integrity of DNA is of immense biological and biomedical significance. Chromatin remodeling factors and helicases are two classes of motor proteins that are involved in modulating the structure of DNA and play essential roles in most nuclear processes, including gene regulation, DNA replication, DNA repair, mitosis and RNA processing. Errors made by these enzymes often lead to complex disorders in humans. We recently identified a new class of motor proteins called annealing helicases, which act to rewind stably unwound DNA. The first identified annealing helicase (HARP) plays a critical role in DNA replication and repair, and mutations in HARP are the cause of a rare disorder known as Schimke immuno-osseous dysplasia (SIOD).
Projects in my lab focus on the study of annealing helicases and other motor proteins. We isolate motor proteins using various protein purification methods and analyze their activities using a number of different assays, including DNA binding, annealing helicase, helicase, chromatin remodeling, and recombination assays. To study the activities of motor proteins in cells, we use various cell-based approaches, including DNA damage/repair assays, siRNA-mediated knockdown, and immunofluorescence. We also use animal models to investigate the link between motor proteins and human diseases.
Yusufzai, T. & Kadonaga, J.T. (2008) HARP Is an ATP-driven Annealing Helicase. Science 322:748-50.
Yusufzai, T., Kong, X., Yokomori, K. & Kadonaga, J.T. (2009) The Annealing Helicase HARP Is Recruited to DNA Repair Sites via an Interaction with RPA. Genes & Dev. 23:2400-4.
For a complete listing of publications click here.