7.3
Cohesins
Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In…
During S-phase of the cell cycle in eukaryotes, chromosomal duplication produces two identical copies of each chromosome called sister chromatids.
The sister chromatids formed are held together by a set of protein complexes called cohesins. The cohesin rings exist as clamps around the sister chromatids at multiple locations along their length, preventing them from drifting apart.
Cohesin complexes contain four subunits: Smc1, Smc3, Scc1, and Scc3. The Smc1 and Smc3 are coiled-coil proteins with a hinge domain at one end and an ATPase head domain at the other end. The hinge domains of Smc1 and Smc3 bind directly to each other, while an Scc1 subunit connected to an Scc3 subunit bridges the head domains of Smc1 and Smc3, forming a ring-like structure.
The hinge domain of the cohesin ring-structure can be triggered to open and close, facilitating cohesin loading on the chromosomes.
As cells progress through mitotic prophase, sister chromatid resolution takes place, involving dissociation of cohesin rings along the chromosomal arms while preserving those bound to the centromere region. The differential removal of cohesins causes the sister chromatids to become partially separated along their arms while remaining bound at their centromere.
Chromatid cohesion at the centromere facilitates the bi-orientation of chromosomes on the mitotic spindle during metaphase, ensuring correct microtubule attachment to the kinetochores of the sister chromatids.
At the onset of anaphase, a protease enzyme, separase, cleaves the Scc1 subunit, leading to the dissociation of cohesin from the chromosome.
Cohesin dissociation permits the segregation of sister chromatids during anaphase, where they are pulled apart by mitotic spindles to opposite poles of the cell, eventually leading to cell division and formation of two daughter cells.
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Q1: What are the four subunits that make up a cohesin complex?
Cohesin complexes contain four subunits: Smc1, Smc3, Scc1, and Scc3. Smc1 and Smc3 are coiled-coil proteins with a hinge domain and an ATPase head domain. The hinge domains bind directly to each other, while Scc1 bridges the head domains of Smc1 and Smc3, forming a ring-like structure that holds sister chromatids together.
Q2: How do cohesins hold sister chromatids together during cell division?
Cohesin rings function as molecular clamps that encircle sister chromatids at multiple locations along their length, preventing them from drifting apart. The ring-like structure formed by the four subunits can open and close at the hinge domain, allowing cohesins to load onto chromosomes during S-phase and maintain sister chromatid cohesion throughout mitosis until anaphase.
Q3: Why is differential cohesin removal important during mitotic prophase?
During mitotic prophase, cohesins are selectively removed from chromosomal arms while those at the centromere remain intact. This differential removal allows sister chromatids to partially separate along their arms while staying bound at the centromere, facilitating proper bi-orientation of chromosomes on the mitotic spindle and ensuring correct microtubule attachment to kinetochores during metaphase.
Q4: What role does separase play in sister chromatid separation?
At the onset of anaphase, the protease enzyme separase cleaves the Scc1 subunit of cohesin complexes, causing the cohesin rings to dissociate from chromosomes. This cleavage permits sister chromatids to segregate during anaphase, where they are pulled apart by mitotic spindles to opposite poles of the cell, eventually leading to cell division.
Q5: How does meiotic cohesin differ from mitotic cohesin?
Meiotic cohesin complexes contain Rec8 instead of Scc1, along with Smc1, Smc3, and Scc3. During Meiosis I, cohesins are removed only from chromosomal arms while remaining at the centromere, allowing homologous chromosomes to separate while sister chromatids stay connected. A protector protein called Shugoshin shields centromeric Rec8 from separase cleavage during this stage.
Q6: What are cohesinopathies and how do they arise?
Cohesinopathies are diseases caused by mutations in genes coding for cohesin subunits or cohesin co-factors, disrupting genomic stability. Cornelia de Lange syndrome causes neurodevelopmental disorders, facial abnormalities, and growth delay, while Roberts syndrome results in craniofacial abnormalities and limb reduction. These conditions demonstrate cohesin's critical role in maintaining proper chromosome segregation.
Q7: How does the hinge domain of cohesin facilitate chromosome loading?
The hinge domain of the cohesin ring-structure can be triggered to open and close, enabling cohesin loading onto chromosomes during S-phase when sister chromatids are formed. This dynamic opening and closing mechanism allows the ring to encircle sister chromatids at multiple locations along their length, establishing the cohesion necessary to prevent chromatid separation until anaphase.