May 1, 2019
Rita Miller will present Biochemistry and Molecular Biophysics Seminar today
Rita Miller, associate professor of biochemistry and molecular biology at Oklahoma State University and program director in the Cellular Dynamics and Function Cluster in the Division of Molecular and Cellular Biosciences, BIO directorate at the National Science Foundation, is the featured speaker for Biochemistry and Molecular Biophysics Seminar on Wednesday, May 1. She will present "Two new ways to regulate chromosomal loss" at 4 p.m. in 120 Ackert Hall.
Miller's research interests are centered on elucidating the molecular mechanisms that control mitotic spindle positioning during cell division and other microtubule dependent processes. Asymmetric positioning of the mitotic spindle is an active process that permits the asymmetric distribution of cell-specificity determinants and the establishment of different cell fates. Incorrect spindle positioning can result in genetic instability due to chromosomal mis-segregation, which is an important component of many cancers. The Miller laboratory uses the model organism Saccharomyces cerevisiae, also known as budding yeast, and is particularly interested in the post-translational mechanisms that regulate spindle positioning. Miller earned a doctorate in cell biology from Northwestern University Medical School, a Bachelor of Science in physiology from Michigan State University and was a postdoctoral fellow in the laboratory of Mark Rose at Princeton University.
Microtubules are dynamic polymers that are critical elements of the mitotic spindle that segregates the genetic material into each daughter cell at cell division. Microtubule attachment to chromosomes is mediated by a multiprotein complex, known as the kinetochore. Stu2p is a conserved a microtubule binding protein that promotes microtubule polymerization. Stu2p is also is involved in microtubule-to-kinetochore attachments, but its regulation and role in kinetochore function is poorly understood. In this talk, Miller describes two new mechanisms through which Stu2p contributes to microtubule attachment to chromosomes. The Miller lab has shown previously that Stu2p binds non-covalently to the SUMO protein, a small ubiquitin-like modifier that covalently attaches to lysines. Stu2p mutants with a reduced ability bind to SUMO display an increased rate chromosome loss, suggesting that sumoylation plays a role in microtubule attachment to chromosomes. Miller also describes three new acetylation sites on Stu2p. Different Stu2p mutants that either inhibit or mimic acetylation also display increases rates of chromosome loss. As Stu2p is conserved from yeast to humans, these findings have implications for several human disease states that display altered rates of chromosome loss, including birth defects and cancer.