Shaping the metaphase chromosome: coordination of cohesion and condensation

Abstract

Recent progress in our understanding of mitotic chromosome dynamics has been accelerated by the identification of two essential protein complexes, cohesin and condensin. Cohesin is required for holding sister chromatids (duplicated chromosomes) together from S phase until the metaphase-to-anaphase transition. Condensin is a central player in chromosome condensation, a process that initiates at the onset of mitosis. The main focus of this review is to discuss how the mitotic metaphase chromosome is assembled and shaped by a precise balance between the cohesion and condensation machineries. We argue that, in different eukaryotic organisms, the balance of cohesion and condensation is adjusted in such a way that the size and shape of the resulting chromosomes are best suited for their accurate segregation.

Micromechanical studies of mitotic chromosomes

“…The results discussed above, combined with conclusions of Marsden & Laemmli (1979), Losada & Hirano (2001), Lavoie et al (2002), Maeshima & Laemmli (2003), Strukov et al (2003), Kireeva et al (2004), Lavoie et al (2004), Polyakov et al (2006), and Sheval and Polyakov (2006), suggest the follow-ing scenario for vertebrate chromosome condensation ( Figure 13). Numbers are approximate, and apply to the human case.…”

“…The larger is the distance between cohesin domains, the greater will be the length compaction. Metaphase cohesin interdomain distances in vertebrates must be much greater than the 15 kb distance observed in yeast; for Xenopus the cohesin density has been estimated to be one per 400 kb (Losada & Hirano 2001). Cohesin interdomain distances should correlate with mitotic loop size, and possibly with convergent transcription domain size (Lengronne et al 2004) and replicon size (Buongiorno-Nardelli et al 1982).…”

Histone Hyperacetylation in Mitosis Prevents Sister Chromatid Separation and Produces Chromosome Segregation Defects

“…These events require dramatic changes in chromatin structure that are achieved through histone tail modifications by chromatinmodifying enzymatic complexes and by the action of several other enzymatic activities such as condensins and cohesins, topoisomerase II, and the securin/separin pathway (reviewed in Hans and Dimitrov, 2001;Losada and Hirano, 2001;Nasmyth, 2002). Our results discover new aspects of the interplay between histone modifications, sister chromatid condensation and cohesion, and chromosome segregation, and they provide new mechanistic insights into the origin of genome instability in mammalian cells.…”

“…However, the majority of chromosomes producing chromatin bridges showed persistent cohesion along sister chromatid arms but proper centromere separation, demonstrating that inhibition of histone deacetylation in mitosis affects chromosome cohesion along chromatid arms more than at the centromere. It is now becoming clear that chromatin dynamics in mitosis is regulated by the coordinated action of cohesin and condensin activities and that condensin loading on DNA promotes cohesin dissociation (Losada and Hirano, 2001;Nasmyth, 2002). It has been proposed that chromosome arm cohesion in mammalian cells is removed in prophase through a separin-independent mechanism and that centromeric cohesion is released by Scc1 cleavage at the metaphase to anaphase transition (Waizenegger et al, 2000).…”

Cell cycle control of spindle elongation

“…37 The linear chromosome compaction ratio in interphase falls between 70-100 in both yeast 32 and mammalian cells. 38,39 For mitotic chromosomes this number is estimated to be 3,000-2,00,000 in vertebrates [39][40][41] but only 140 in S. cerevisiae 32 and 700 in S. pombe. 42 Thus, the degree of chromosome compaction in mitosis compared to interphase rises dramatically in higher eukaryotes.…”