CPM Seminar

How cells build stereotyped molecular machines

Jackie Vogel

Department of Biology
McGill University

It is essential to accurately partition DNA during the division of biological cells. The mitotic spindle performs this function in eukaryotic cells. The spindle is a mechanically coupled and stereotyped biological machine with a well-defined parts list; microtubules, DNA (chromosomes), proteins that act as force-generators (molecular motors) or couple microtubules to chromosomes or each other, and signaling proteins (for example cyclin dependent kinase; Cdk1) which provide temporal and spatial control. Spindles in both budding yeast and human cells have two common design features; (1) microtubules that project from the spindle poles and attach to chromosomes, promoting the directed movement of chromosomes towards the spindle poles and (2) pairs of microtubules projecting from opposite poles which undergo anti-parallel sliding and drives spindle elongation. In the case of budding yeast, the system is very minimal- one microtubule attaches to each of the 16 duplicated chromosome (32), and 3-4 pairs of anti-parallel microtubules. Both sets of microtubules are critical for forming a functional bi-polar spindle. We use this simple system to characterize the roles of specific molecules in this process. We propose a mechanism by which each microtubule can behave independently of its neighbors during spindle assembly and adopt a specific and irreversible fate, leading to a final stereotyped structure.