Jaspersen Lab Sue Jaspersen, Ph.D. Assistant Investigator slj@stowers-institute.org

     Accurate transmission of genetic and epigenetic information during cell division is critical for the development and survival of organisms. In eukaryotic cells, both mechanisms of inheritance depend on non-random positioning of chromosomes in the nucleus. Research in my lab is focused on understanding the function that a conserved family of inner nuclear envelope integral membrane proteins, known as the SUN (Sad1 UNC-84 homology) proteins, plays in chromosome positioning within the nucleus during interphase and in chromosome distribution during mitosis.

     We use the genetically tractable budding yeast Saccharomyces cerevisiae as a model system for our studies. In budding yeast, MPS3 encodes the sole SUN protein. We have shown that Mps3 is an essential component of the yeast spindle pole body (the functional equivalent of the centrosome) where it plays a role in the structural integrity of the organelle through interactions with other integral membrane proteins. Due to its function at the spindle pole body, Mps3 is required for accurate chromosome segregation.

     More recently, we isolated non-conditional mutants in MPS3 that do not have spindle pole body or chromosome segregation defects. Instead, analysis of these mutants revealed that Mps3 has a previously unrecognized role in regulating telomere positioning and gene inactivation in mitotic cells due to its ability to recruit silent-information regulator proteins to the nuclear periphery. In addition to its function in telomere tethering at the nuclear membrane, our observations that Mps3 genetically and biochemically interacts with several classes of chromosome binding proteins: histones and histone acetyltransferases/deacetylases, certain kinetochore components, DNA polymerase/repair proteins and nuclear pore complex subunits, transcriptional regulators and telomere binding proteins, suggests that Mps3 many play a more general role in chromosome structure and gene regulation at the nuclear envelope.

     Current and future studies in the lab are aimed at testing the function of Mps3, and other SUN proteins, in DNA damage repair, DNA recombination, sister chromosome cohesion and gene transcription and analyzing the role that Mps3-dependent recruitment to the nuclear periphery plays in these processes. We are also interested in studying how Mps3’s interaction with chromosomes is regulated to occur at specific times during cell division. Our studies will help elucidate how the three-dimensional organization of chromosomes within the nucleus can affect gene expression and the maintenance of genomic stability.

Academic Appointment: Assistant Professor, Department of Molecular and Integrative Physiology, The University of Kansas School of Medicine