The condensation of interphase chromatin to form the discrete packages of DNA for segregation during mitosis is one of the more dramatic events in the cell cycle. The metaphase chromosome in metazoans is thought to be formed by a series

The condensation of interphase chromatin to form the discrete packages of DNA for segregation during mitosis is one of the more dramatic events in the cell cycle. The metaphase chromosome in metazoans is thought to be formed by a series of DNA coiling events that transform the basic 11 nanometer nucleosome fiber into ever more complex and compacted loops, giving rise to a series of fibers approx. 30 nanometers, 300 nanometers and 700 nanometers in diameter (Gasser, 1995; Paulson and Laemmli, 1977; Widom and Klug, 1985). Condensed chromosomes are often differentiated into discrete zones, visualized by characteristic banding patterns in response to a particular dye or stain. The ability of certain regions to stay condensed throughout the cell cycle (forming the interphase heterochromatin), while other regions go through rounds of condensation and decondensation, demands both spatial and temporal regulation of condensation. Many lines of evidence imply that condensation must be determined at least in part by features of the DNA itself (see, for example, Benos et al., 2000) and the enzymatic activities of topoisomerases and classes of special folding proteins (Hirano, 1999; Koshland and Strunnikov, 1996). The key outstanding issues are how many levels of regulation exist, and to what extent the differentiated structure of the condensed chromosomes depend upon specialized sequence-dependent DNA:protein interactions. The phenotypes of mutant SMC genes (structural maintenance of chromosomes) (Lieb et al., 1998; Strunnikov et al., 1993) and the biochemical studies of the 13S condensin complex from Xenopus(Hirano et al., 1997; Kimura et al., 1998) have provided deep insights into the mechanisms of chromosomal condensation. 13S condensin is required for a sembly of what appear to be (at low resolution) mitotic-like chromosomes in a Xenopuscell-free extract. Significantly, purified condensin when combined with a type I topoisomerase can reconfigure circular DNA into an ordered structure with a positive global writhe in an ATP-dependent manner (Kimura et al., 1999). Given the high abundance and biochemical activities of this complex, Kimura et al. suggest that positive olenoidal supercoiling of a nucleosomal fiber (or a higher order fiber) by the condensin complex is a key mitosis-specific strategy for chromosomal folding (Kimura et al., 1999). Condensin is clearly necessary for chromosomal folding, but it may not be sufficient. S-phase progression and the completion of DNA replication, with concomitant production of sister chromatid fibers, is not necessary for a certain level of condensation. In G1 cells fused to metaphase cells, the membrane of the G1 nucleus breaks own and its chromosomes undergo premature chromosomal condensation (PCC) without passage through S phase (Rao and Hanks, 1980). Moreover, decondensed Xenopus sperm chromosomes undergo condensation in a cell-free extract when provided the 13S condensin complex, ATP and topoisomerases without detectable DNA replication (Hirano, 1999). 1697 Development 128, 1697-1707 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV5901