35.3
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 cohesins and what role do they play in cell division?
Cohesins are protein complexes that hold sister chromatids together after DNA replication. They maintain chromosomal cohesion throughout the cell cycle, ensuring proper chromosome segregation during mitosis and cytokinesis. Without cohesins, chromosomes would separate prematurely, leading to genetic instability and cell death.
Q2: How do cohesins maintain the structure of replicated chromosomes?
Cohesins form ring-like structures that encircle sister chromatids, creating physical connections between them. These protein complexes load onto DNA during replication and remain attached until anaphase, when they are cleaved to allow chromosome separation. This mechanism ensures sister chromatids stay paired until the appropriate time for division.
Q3: What happens when cohesins fail to function properly during cell division?
When cohesins malfunction, sister chromatids separate prematurely or fail to separate at all, causing chromosomal abnormalities. This leads to aneuploidy, where cells receive incorrect chromosome numbers, resulting in genetic instability, potentially cell death, or cancer development. Cohesin dysfunction is a significant cause of chromosomal disorders.
Q4: How do cohesins differ in their function between mitosis and meiosis?
In mitosis, cohesins hold sister chromatids together until anaphase. In meiosis, cohesins maintain homologous chromosome pairing during meiosis I, then sister chromatid cohesion during meiosis II. This dual function ensures proper segregation of both genetic material and chromosome number reduction in gametes.
Q5: When do cohesins load onto DNA and when are they removed?
Cohesins load onto DNA during S phase following replication, establishing sister chromatid cohesion. They remain bound throughout G2 and early mitosis. During anaphase, separase protease cleaves cohesin subunits, allowing sister chromatids to separate and move to opposite poles of the dividing cell.
Q6: Why is chromosomal cohesion essential for genetic stability?
Chromosomal cohesion prevents premature chromosome separation and ensures each daughter cell receives identical genetic material. Proper cohesin function maintains accurate chromosome segregation, preventing mutations and chromosomal rearrangements that could compromise cell viability. This process is fundamental to maintaining genetic integrity across cell generations.