I. Separating Duplicated Chromosomes
II. Understanding Mitosis through Experimentation
III. Moving Chromosome to the Spindle Poles: the Mechanisms of Anaphase A
Part I: Separating Duplicated Chromosomes
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The goal of these three talks is to define the problems that a cell faces as it prepares for division and to describe some of the ways it solves them. In Part 1, both the length and amount of DNA are presented as problems for chromosome segregation, particularly in eukaryotic cells. The actions of cohesins and of chromosome condensation are described as solutions. The mitotic machinery is introduced, including its diversity of form across phylogeny, however, the features that appear to be conserved are emphasized. This lecture may be useful for upper level undergraduate and graduate courses discussing mitosis and cell division.
The second lecture describes some key experiments showing the dynamics of a formed mitotic spindle and the ways these may contribute to accurate chromosome motion. Experiments that reveal aspects of the processes by which chromosomes attach to the spindle are presented. Mitotic motors are introduced and discussed in the light of what they probably do and do not accomplish to effect chromosome motion, including acting to improve the accuracy of chromosome segregation.
The third lecture presents evidence, largely from McIntosh's lab, that shows how microtubule depolymerization can move chromosomes in vitro and explores the nature of some of the protein complexes that can couple chromosomes to microtubules and take advantage of this reaction.
Richard McIntosh is currently a Distinguished Professor Emeritus at the University of Colorado Boulder. He earned his bachelor's and doctorate degrees from Harvard University in Physics and Biophysics, respectively. He taught cell biology at that institution briefly, then moved to the University of Colorado at Boulder, where he has worked ever since. His principal scientific interest is the mitotic spindle, i.e., the cellular machinery that segregates duplicated chromosomes in preparation for cell division. McIntosh's lab has answered a number of questions on spindle structure and function using electron microscopy based 3-D tomography.
McIntosh has served as President of the American Society for Cell Biology and has been appointed an American Cancer Society Research Professor. He is a member of the American Academy of Arts and Sciences and the National Academy of Sciences. McIntosh is also a passionate advocate for biology research in Africa. He has spent a sabbatical year in Uganda, and directed courses in Tanzania and in Ghana.
- Sue Biggins iBioSeminar: The Kinetochore and Chromosome Segregation
- Abby Dernburg iBioSeminar: Chromosome Dynamics During Meiosis
- Shinya Inoue iBioMagazine: The Dynamic Mitotic Spindle
- Tim Mitchison iBioSeminar: Self-Organization of Microtubule Assemblies
- David Morgan iBioSeminar: Controlling the Cell Cycle: Introduction
- Thomas Pollard: Cell Motility and Cytokinesis
- Ron Vale iBioSeminar: Introduction to Molecular Motors
Alberts et al., 2007 Molecular Biology of the Cell, fifth edition Chapters 16,17 Garland Press.
McIntosh, J.R., et al. (2002). "Chromosome-microtubule interactions during mitosis." Annu Rev Cell Dev Biol 18: 193-219.
Cheeseman, I.M. and A. Desai (2008). "Molecular architecture of the kinetochore-microtubule interface." Nat Rev Mol Cell Biol 9(1): 33-46.
Rieder, C.L. and E.D. Salmon (1998). "The vertebrate cell kinetochore and its roles during mitosis." Trends Cell Biol 8(8): 310-8.
More Specific Readings McIntosh, J.R. et al. (2008) "Fibrils connect microtubule tips with kinetochores: a mechanism to couple tubulin dynamics to chromosome motion." Cell 135(2): 322-33.
Grishchuk, E.L. et al. (2008). "Different assemblies of the DAM1 complex follow shortening microtubules by distinct mechanisms." Proc Natl Acad Sci U S A 105(19): 6918-23.
Grishchuk, E.L. et al. (2008). "The Dam1 ring binds microtubules strongly enough to be a processive as well as energy-efficient coupler for chromosome motion." Proc Natl Acad Sci U S A 105(40): 15423-8.
Grissom, P. M., T. A. Fiedler, et al. (2008). "Kinesin-8 from Fission Yeast: a Heterodimeric, Plus End-Directed Motor that Can Couple Microtubule Depolymerization to Cargo Movement." Mol Biol Cell. 10.1091/mbc.E08-09-0979