Step 2: Axial compression In addition to loop formation, polymer models require a second step to accurately simulate the formation of cylindrical chromosomes: compression along the longitudinal chromosome axis. Quantitative imaging experiments of fluorescently labeled histones are indeed consistent with Bioessays 37: 755766, 2015 The Authors. Bioessays published by WILEY Periodicals, Inc. …. Prospects & Overviews M. Kschonsak and C. H. Haering TSU68 web assembled in Xenopus egg extracts in which condensin II has been depleted or prevented to load onto chromosomes. In contrast, normal-shaped prometaTopo II phase chromosomes can sometimes be observed in human cells depleted of condensin II subunits by RNA interference. Condensin II In these cases, it might be possible that Condensin II residual amounts of condensin II, which have escaped depletion, are sufficient for the first two steps of chromosome conLinear looping densation. Aberrant condensin II loading Cohesin onto chromosomes might in return result in A) the shorter and thicker metaphase chromosomes observed in MCPH1 patient cells. Consistent with a contribution of topo C) Early Prophase IIa to the axial compression step is the observation that the enzyme accumulates on the chromatid axes in cultured human Late Prophase G2 phase cells during prophase. Knockdown of topo IIa in cultured chicken cells results in longer and thinner metaphase chromoAxial compression somes and depletion of topo IIa in Metaphase Xenopus egg extracts blocks the transD) formation of sperm chromatin into M phase chromosomes. Even though depletion or inhibition of topo IIa in human cells Condensin I increases the fraction of partially condensed chromosomes, normal-shaped metaphase chromosomes form eventually. Likewise, inhibition of topo IIa with an antibody or a small molecule inhibitor has no effect on mitotic chromoLateral compression somes once they have been assembled in Xenopus egg extracts. These findings B) Review essays Bioessays 37: 755766, 2015 The Authors. Bioessays published by WILEY Periodicals, Inc. 761 M. Kschonsak and C. H. Haering Prospects & Overviews …. formation of mitotic chromosomes Chromosomes assembled in Xenopus egg extracts contain approximately five times the amount of condensin I compared to condensin II. Reducing the proportion of condensin I results in the formation of shorter and wider chromosomes. Condensin I has hence been suggested to reduce the chromosome diameter. Support for this proposal also comes from the report that the caspase-dependent degradation of the kleisin subunit of condensin I in human cells, arrested by spindle poisons over long periods of time, results in an increase in chromosome width. Yet, the width of human chromosome arms does not appear to change PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19808515 once condensin I binds after NEBD, suggesting that a lateral compaction step might occur in some cell types but not in others. However, it might still be conceivable that, even in HeLa cells, condensin I is essential to “reel in” individual 
chromatin fibers that protrude from the chromatid cylinder, for example those that are still connected to the other sister chromatid by cohesin complexes that escaped the prophase pathway. Such a scenario could explain how condensin I contributes to the complete removal of cohesin from chromosome arms in these cells. In addition, condensin I binding is thought to mechanically stabilize the chromatids, since centromeric regions that come under tension by their attachment to spi