Chromosomes Progress to Metaphase in Multiple Discrete Steps via Global Compaction/Expansion CyclesLiang, Z., Zickler, D., Prentiss, M., Chang. F.S., Witz, G., Maeshima, K., Kleckner, N. Cell, 161, 1124-1137 (2015). DOI:10.1016/j.cell.2015.04.030
Mammalian mitotic chromosome morphogenesis was analyzed by 4D live-cell and snapshot deconvolution fluorescence imaging. Prophase chromosomes, whose organization was previously unknown, are revealed to comprise co-oriented sister linear loop arrays displayed along a single, peripheral, regularly kinked topoisomeraseII /cohesin /condensinII axis (Fig a). Thereafter, rather than smooth, progressive compaction as generally envisioned, progression to metaphase is a discontinuous process involving chromosome expansion as well as compaction. At late prophase (Fig b), dependent on topoisomerase II and with concomitant cohesin release, chromosomes expand, axes split and straighten, and chromatin loops transit to a radial disposition around now-central axes. Finally, chromosomes globally compact, giving the metaphase state (Fig c). These patterns are consistent with the hypothesis that the molecular events of chromosome morphogenesis are governed by accumulation and release of chromosome stress, created by chromatin compaction and expansion. Chromosome state could evolve analogously throughout the cell cycle.
Two sister DNAs are shown in red and blue. The chromosome axis is in yellow. (a) mid-prophase; two sister chromatids are condensed with a single axis (yellow), but still mixed. (b) late-prophase; with expansion, two sisters and their axes are segregated. (c) metaphase; Further condensation and separation of the two sisters occur in metaphase.