Cohesin Complex

The cohesin complex is a chromosome-associated protein complex with multiple subunits that is highly conserved in eukaryotes and has close homologs in bacteria. Cohesin mediates cohesion between replicated sister chromatids and is therefore essential for chromosome segregation in dividing cells. Furthermore, cohesin is also required for efficient repair of damaged DNA and has important functions in regulating gene expression in both proliferating and post-mitotic cells. Mutations in the proteins that form the cohesin ring, as well as in the proteins necessary for loading DNA with the cohesin complex, can cause diseases grouped under the term "cohesinopathies" (McNairn AJ et al. 2008). The cohesinopathies include Cornelia de Lange syndrome.

The sister chromatids of chromosomes are linked from the moment of their formation during DNA replication until cell division. The cohesin-protein complex holds the two sister chromatids together (K. Nasmyth et al. 2005). Here, the cohesin-protein complex forms a kind of ring around the DNA strand (Haering CH et al. 2008).

The microtubules are also attached to the chromosomes by a protein complex. The fixation of the microtubules to the kinetochores is monitored by special checkpoint proteins.

Since the sister chromatids are encompassed by cohesin complexes, proper bipolar attachment of the sister kinetochores to opposite spindle poles leads to a kind of tug-of-war: the shortening microtubules try to pull the kinetochores apart, while the cohesin rings prevent this. The resulting tensile stress is measured by special "monitoring" proteins. Kinetochores without attached microtubules are subsequently detected by the checkpoint proteins; cell division is arrested and not released until all chromosomes are attached to microtubules. After all sister chromatids are fixed to the opposite spindle poles, the checkpoint is inactivated.

This process leads to the activation of a specific protease, separase. The separase dissolves these cohesins again in anaphase (mitosis). This in turn allows the sister chromatids to be pulled from the spindle fibers to the cell poles.

1. K. Nasmyth et al. (2005) The structure and function of SMC and kleisin complexes. Annual Review of Biochemistry 74, 595-648
2. Haering CH et al (2008) The cohesin ring concatenates sister DNA molecules. Nature 454: 297-301.
3. McNairn AJ et al. (2008) Cohesinopathies: one ring, many obligations. Mutation Research 647: 103-111