In Aspergillus, genetic interactions between BIMD and the Smc3p ortholog SUDA suggest that BIMD may physically or functionally interact with 14S cohesin ( Holt and May 1996). In fission yeast, the Scc2p ortholog Mis4p and the Eco1p/Ctf7p-related protein Eso1p are also required for cohesion ( Furuya et al. However, these proteins are not essential for the maintenance of cohesion in G2 and are not part of 14S cohesin. 2000) and that the establishment of cohesion in S phase depends on Eco1p/Ctf7p ( Skibbens et al. Experiments in budding yeast indicate that the binding of 14S cohesin to DNA in S phase requires Scc2p and Scc4p ( Ciosk et al. 1999), consistent with the notion that the binding of the cohesin complex to replicated DNA is required for the establishment and maintenance of cohesion.Ī number of additional proteins have been shown to have a role in cohesion, some possibly by interacting with 14S cohesin. In budding yeast, all four cohesin subunits are associated with chromatin from S phase until the onset of anaphase ( Guacci et al. Members of this family were first identified in scaffold preparations of metaphase chromosomes ( Lewis and Laemmli 1982) and are now known to be required for a variety of chromosomal functions, including cohesion, condensation, recombination, and gene dosage compensation (reviewed in Jessberger et al.
![prophase picture prophase picture](http://biolo1100.nicerweb.com/Locked/media/ch08/08_14_02.jpg)
Smc1p and Smc3p belong to the SMC protein family, which is represented in bacteria and eukaryotes. The yeast complex contains the subunits Smc1p, Smc3p, Scc1p/Mcd1p, and Scc3p ( Strunnikov et al. In budding yeast and Xenopus, four or five cohesin proteins form a 14S cohesin complex ( Losada et al. Although it is not yet known whether cohesins directly connect sister chromatids or mediate cohesion indirectly, it is tempting to speculate that the APC-dependent removal of cohesins liberates sisters for poleward movement and thereby initiates anaphase (reviewed by Koshland and Guacci 2000 Nasmyth et al. These proteins are called cohesins because they are required for sister chromatid cohesion in both yeast and Xenopus. In budding yeast, the APC initiates anaphase by activating a pathway that removes chromosomal proteins from sister chromatids. In presumably all eukaryotes, this event depends on activation of the anaphase-promoting complex (APC), a cell cycle–regulated ubiquitin–protein ligase that targets proteins for destruction by the 26S proteasome (reviewed by Morgan 1999 Peters 1999). To initiate anaphase, sister chromatid cohesion has to be dissolved. Sister chromatid cohesion therefore enables the equal segregation of the duplicated genome to forming daughter cells long after DNA replication has occurred. Cohesion is a prerequisite for the bipolar attachment of chromatid pairs to the spindle apparatus in mitosis. In eukaryotic cells, duplicated DNA molecules (“sisters”) remain physically connected by cohesion from the time of their synthesis in S phase until they are separated in anaphase. These results suggest that vertebrate cohesins are regulated by a novel prophase pathway which is distinct from the APC pathway that controls cohesins in yeast. Cohesins can also dissociate from chromatin in the absence of cyclin-dependent kinase 1 activity. Reconstitution of this process in mitotic Xenopus extracts shows that cohesin dissociation does neither depend on cyclin B proteolysis nor on the presence of the APC. The bulk of SA1- and SA2-containing complexes and PDS5 are chromatin-associated until they become soluble from prophase to telophase. These complexes interact with PDS5, a protein whose fungal orthologs have been implicated in chromosome cohesion, condensation, and recombination.
![prophase picture prophase picture](https://useruploads.socratic.org/y07dg2mXQCWP5QQORzuA_prophase_1.jpg)
![prophase picture prophase picture](http://medicalpicturesinfo.com/files/wp-content/uploads/2011/11/Dermatofibroma-3.jpg)
SA1 is also a subunit of 14S cohesin in Xenopus.
![prophase picture prophase picture](https://image1.slideserve.com/1985141/slide4-l.jpg)
Both complexes contain SMC1, SMC3, SCC1, and either one of the yeast Scc3p orthologs SA1 and SA2. To study their mitotic regulation we have purified two 14S cohesin complexes from human cells. In vertebrates, cohesins dissociate from chromosomes already in prophase. In budding yeast, the anaphase-promoting complex (APC) pathway initiates anaphase by removing cohesins from chromosomes. This cohesion depends on a complex of proteins called cohesins. In eukaryotes, sister chromatids remain connected from the time of their synthesis until they are separated in anaphase.