The cohesin complex is composed of SMC1, SMC3, a kleisin subunit (Scc1) and a fourth subunit (Scc3) with no obvious structural motifs. Equally important, the precise geometry of the five subunits in each complex remains to be determined.Įukaryotic cells have another SMC protein complex, known as cohesin, that is involved in sister chromatid cohesion during mitosis and meiosis ( Losada and Hirano, 2005 Nasmyth and Haering, 2005). Condensin II has not yet been visualized by electron microscopy, and it is unknown to what extent its overall architecture is similar to that of condensin I. In fact, it has been found that CAP-D3 and CAP-G2 have HEAT repeats, whereas CAP-H2 belongs to the kleisin family. Although sequence similarities between the non-SMC subunits of condensin I and condensin II are hardly detectable by simple alignment methods, they are related to each other. This complex shares the same SMC core subunits with condensin I, but has a distinct set of non-SMC subunits (CAP-D3, CAP-G2 and CAP-H2). Recent studies have shown that higher eukaryotes possess a second condensin complex, referred to as condenisn II ( Ono et al, 2003 Yeong et al, 2003). As judged by electron microscopy, this subcomplex binds to the head domains of the SMC2–SMC4 dimer, and leads to the formation of a 13S holocomplex that displays a ‘lollipop-like’ structure ( Anderson et al, 2002). The three non-SMC subunits associate with each other to form an 11S subcomplex ( Kimura and Hirano, 2000). Among the three non-SMC subunits, two (CAP-D2 and CAP-G) contain multiple HEAT repeats implicated in protein–protein interactions ( Neuwald and Hirano, 2000), and the third (CAP-H) belongs to the kleisin family of proteins ( Schleiffer et al, 2003). SMC2 and SMC4 form a heterodimer that adopts a V-shaped structure with two long coiled-coil arms, each containing an ATP-binding cassette (ABC) head domain at the distal end ( Melby et al, 1998 Anderson et al, 2002). The two core subunits, SMC2/CAP-E and SMC4/CAP-C, belong to a conserved family of chromosomal ATPases, known as structural maintenance of chromosomes (SMC) proteins ( Hirano and Mitchison, 1994 Saitoh et al, 1994 Saka et al, 1994 Strunnikov et al, 1995). The canonical condensin complex (condensin I) is composed of five subunits ( Hirano et al, 1997 Sutani et al, 1999). Accumulating lines of evidence suggest that a class of multisubunit complexes, known as condensins, plays an important role in this process by collaborating with other chromosomal components ( Strunnikov, 2003 Hirano, 2005). Our results shed new light on the architecture and dynamics of this highly elaborate machinery designed for chromosome assembly.Ĭhromosome condensation is an essential prerequisite for the faithful segregation of genetic information, and is therefore crucial in maintaining genome integrity during mitosis and meiosis. Cleavage pattern of SMC2 by limited proteolysis is changed upon its binding to ATP or DNA. ATP has little, if any, effects on the assembly and integrity of condensin. No direct interactions are detectable between the SMC dimer and the HEAT subunits, indicating that the kleisin subunit acts as the linchpin in holocomplex assembly. We show that both condensin I and condensin II have a pseudo-symmetrical structure, in which the N-terminal half of kleisin links the first HEAT subunit to SMC2, whereas its C-terminal half links the second HEAT subunit to SMC4. Here we use recombinant human condensin subunits to determine their geometry within each complex. Each complex contains a pair of structural maintenance of chromosomes (SMC) ATPases, a kleisin subunit and two HEAT-repeat subunits.
Vertebrate cells possess two different condensin complexes, known as condensin I and condensin II, that play a fundamental role in chromosome assembly and segregation during mitosis.
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