Condensins, Cohesins, and Chromosome Architecture: How to Make and Break a Mitotic Chromosome

that interphase nuclei could be converted to mitotic University of Edinburgh chromosomes only if topoisomerase II was endoge-Institute of Cell and Molecular Biology nously present or added back after depletion of the King's Buildings extract. Edinburgh EH9 3JR More recently, a similar convergence of data from Scotland divergent approaches has revealed the importance of the SMC (structural maintenance of chromosomes, formerly called stability of mini chromosomes) family of proteins in mitotic chromosome structure and function. The orderly packaging of DNA into chromosomes in Discovered originally in S. cerevisiae and now known preparation for mitosis is a structural problem common to be present in species from mycoplasma to mammals, to all cells. The DNA in metaphase chromosomes of the SMCs comprise at least four distinct subfamilies higher eukaryotic cells is compacted nearly 10,000-fold (reviewed in Koshland and Strunnikov, 1996; also see in length (a packaging ratio 20-to 100-fold greater than Table 1). smc1 mutants (S. cerevisiae) had a dramatic in interphase [Trask, et al., 1993]). Thus, a hypothetical increase in the rate of chromosome loss as well as a metaphase chromosome 1 cm in length would have defect in nuclear division, while smc2 mutants exhibited about 100 m of DNA within it, with the diameter of each a defect in chromosome segregation and partial chro-sister chromatid being about 1 mm. This condensation mosome decondensation in cells arrested in mitosis. is all the more amazing when one considers that the This theme was reiterated in S. pombe, where it was products of replication are intertwined, and that the con-shown that the Cut3 and Cut14 (for cell untimely torn) sequences of improper condensation or resolution of SMC proteins were essential for chromosome conden-decatenation are dire to the cell. sation and segregation; additionally, since cut3 and Putting the Usual Subjects on the Scaffold Just how chromosomes are ordered has inspired nu-topoisomerase II mutants were synthetically lethal, this merous models, ranging from random spaghetti-like suggested that these proteins may cooperate in chro-folding to successive orders of helical coiling of the DNA mosome condensation. The nematode DPY-27 SMC is fibre (starting with DNA coiled around the nucleosome), involved in dosage compensation and specifically coats to the involvement of a specific subset of nonhistone the X chromosome in somatic cells. In chicken, the proteins anchoring loops of chromatin (reviewed in Earn-abundant Sc2 component of the chromosome scaffold shaw, 1991). Electron micrographs published two de-is an SMC protein. …