Question 1

What are the four subunits that make up a cohesin complex?

Accepted Answer

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.

Question 2

How do cohesins hold sister chromatids together during cell division?

Accepted Answer

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.

Question 3

Why is differential cohesin removal important during mitotic prophase?

Accepted Answer

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.

Question 4

What role does separase play in sister chromatid separation?

Accepted Answer

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.

Question 5

How does meiotic cohesin differ from mitotic cohesin?

Accepted Answer

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.

Question 6

What are cohesinopathies and how do they arise?

Accepted Answer

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.

Question 7

How does the hinge domain of cohesin facilitate chromosome loading?

Accepted Answer

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.

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