Mary C. Dasso, Ph.D.
Section on Cell Cycle Regulation
Building 49, Room 5A30
49 Convent Drive
Bethesda, MD 20814
Mitotic Regulation in Higher Eukaryotes by Ran and SUMO-1
We are interested in mechanisms of chromosome segregation. Defects in chromosome segregation lead to aneuploidy, the condition of an abnormal number of chromosomes, which in turn may drive tumor formation. To elucidate these mechanisms, we study the mitotic roles of proteins associated with the interphase nuclear pore complex (NPC). NPCs are conduits for nucleocytoplasmic trafficking and organize other nuclear processes, such as gene expression and the repair of DNA damage. Surprisingly, many NPC components (nucleoporins) localize to mitotic kinetochores, the proteinaceous structures that attach sister chromatids to mitotic spindles and mediate their segregation into daughter cells at anaphase. The Ran GTPase and SUMO conjugation pathways are functionally and physically linked to each other and to NPCs. The Ran GTPase controls many cellular activities, including nucleocytoplasmic trafficking, nuclear assembly, and cell cycle progression. SUMO proteins are a family of ubiquitin-like proteins that become covalently conjugated to cellular targets. The pathways are indispensable for mitotic spindle assembly and kinetochore function. The ultimate goal of our studies is to understand the mitotic roles of these proteins, discover how they are coordinated, and determine how such coordination enhances the accurate distribution of chromosomes during mitosis.
Dr. Mary Dasso received her B.A. in Chemistry from the Robert D. Clark Honors College at the University of Oregon. She was awarded a Marshall Scholarship for studies at the University of Cambridge (King’s College), where she obtained her Ph.D. in Biochemistry. She was a Damon Runyon Cancer Research Fund Fellow at the University of California in La Jolla, California. She became a tenure-track investigator within the Laboratory of Molecular Embryology in the NICHD in 1994, and received tenure in 2000. She is currently a Senior Investigator in the Laboratory of Gene Regulation and Development. Dr. Dasso’s studies focus on the regulation of cell division in higher eukaryotes.
Mishra RK, Chakraborty P, Arnaoutov A, Fontoura BM, Dasso M. The Nup107-160 complex and gamma-TuRC regulate microtubule polymerization at kinetochores. Nat Cell Biol. 2010;12(2):164-9.
Arnaoutov A, Dasso M. Enzyme regulation. IRBIT is a novel regulator of ribonucleotide reductase in higher eukaryotes. Science. 2014;345(6203):1512-5.
Ryu H, Gygi SP, Azuma Y, Arnaoutov A, Dasso M. SUMOylation of Psmd1 controls Adrm1 interaction with the proteasome. Cell Rep. 2014;7(6):1842-8.
Zhang MS, Arnaoutov A, Dasso M. RanBP1 governs spindle assembly by defining mitotic Ran-GTP production. Dev Cell. 2014;31(4):393-404.
Markossian S, Arnaoutov A, Saba NS, Larionov V, Dasso M. Quantitative assessment of chromosome instability induced through chemical disruption of mitotic progression. Cell Cycle. 2016;15(13):1706-14.