Advances in imaging reveal novel insights into the mechanisms promoting accurate chromosome segregation in mitosis and meiosis

Abstract

The most important outcome of both mitotic and meiotic cell divisions is the accurate segregation of chromosomes. Failure to properly separate sister chromatids during mitosis as well as either homologues or sister chromatids during meiosis I and II, respectively, results in aneuploidy that contributes to tumorigenesis and causes miscarriages, infertility, and birth defects. Speakers at the Mitosis and Meiosis Minisymposium at the ASCB 2010 meeting highlighted new and exciting mechanisms that promote faithful chromosome segregation during these two cell division programs. Duane Compton (Dartmouth Medical School) started the mitosis section by describing recent work using fluorescence dissipation after photoactivation of green fluorescent protein–tagged tubulin to measure the dynamic attachment of microtubules to kinetochores (kMTs). His work showed that molecular changes in the composition of the outer kinetochore generate optimal kMT attachment dynamics during mitotic progression so that kMTs are stable enough to satisfy the spindle assembly checkpoint but not so stable that they prevent the correction of attachment errors. Alexey Khodjakov (Wadsworth Center) showed data using three-dimensional video microscopy that permits him to track the location of single sister kinetochore pairs relative to centrosomes with unprecedented temporal resolution. His work showed how chromosome movements and chromosome arm orientation relative to spindle poles work together to position chromosomes optimally for attachment of kinetochores to spindle microtubules within the brief time window in the early stages of mitosis. Andrew Powers (University of Washington), the recipient of the Norton B. Gilula Award, presented his work using laser trapping to measure the interaction of kinetochores with microtubules. He demonstrated that there is a direct relationship between the force applied to a microtubule and the lifetime that kinetochore complexes hold onto kMT ends, analogous to a Chinese finger trap. The first speaker in the meiosis section was Jennifer Fung (University of California, San Francisco). She described the development of live cell imaging techniques to measure the kinetics of the formation of the synaptonemal complex that assembles between homologous chromosomes during meiosis in most organisms from yeast to humans. Using high-resolution imaging, she showed that, in budding yeast, synapsis proceeds at a rate of ∼30 nm/min and is continuous, with the number of nucleation sites acting as a limiting factor in the speed of this process. Monica Colaiacovo (Harvard Medical School) addressed the poorly understood regulation of establishment and maintenance of sister chromatid cohesion during meiosis in Caenorhabditis elegans. By combining high-resolution imaging and genetic analyses, she demonstrated that LAB-1, a functional analog of Shugoshin, acts to localize cohesin members such as SMC-3 by antagonizing cohesin-destabilizing factors early in prophase, thereby promoting normal progression of chromosome pairing, synapsis, and recombination. Julien Dumont (Institut Curie, Paris) addressed the important question of how chromosomes segregate in the absence of astral microtubules in meiosis. His studies in the context of the C. elegans holocentric chromosomes revealed that microtubules form exclusively between separating chromosomes, suggesting an “inside-out” kinetochore-independent mechanism driving meiotic anaphase chromosome separation. In summary, a theme that emerged from these talks is that improvements in imaging modes and resolution (spatial and temporal) are revealing insights into the mechanisms that drive accurate chromosome segregation in mitosis and meiosis.