35.10
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chrom…
At the end of metaphase, the bi-oriented chromosomes align at the metaphase plate. During this phase, the cohesin protein ring-complexes hold the sister chromatids together at the centromere region and prevent them from being pulled apart.
Metaphase to anaphase progression is triggered by the cyclin-Cdk-induced phosphorylation of a multisubunit, ubiquitin ligase enzyme – the anaphase-promoting complex, also known as the cyclosome or APC/C. Phosphorylated APC/C binds to a protein, Cdc20, forming an active complex.
The active APC/C complex recognizes an inhibitory protein called securin that is bound to a protease enzyme called separase. Prior to this recognition, securin inhibits the activity of separase.
The active APC/C complex tags securin with the protein ubiquitin, targeting it for proteasomal degradation. Destruction of securin releases separase.
The cyclin-Cdk complex also negatively regulates unbound separase activity through inhibitory phosphorylation.
The active APC/C complex causes the ubiquitination of cyclins, targeting them for proteasomal degradation. The destruction of cyclin removes the enzymatic activity of cyclin-dependent kinases or Cdks.
Inactivation of Cdks allows phosphatase enzymes to dephosphorylate separase and prevents Cdk-mediated inhibitory re-phosphorylation of separase. Dephosphorylation allows the separase enzyme to cleave the cohesin ring-complex that holds sister chromatids together.
Cohesin cleavage results in the absolute loss of sister-chromatid cohesion, marking the transition from metaphase to anaphase. The loss of cohesion permits the sister chromatids to separate and move to opposite poles of the spindle.
View the full transcript and gain access to JoVE Core videos
Q1: What happens to sister chromatids during cell division?
Sister chromatids are identical DNA copies held together at the centromere. During mitosis and cytokinesis, they separate to ensure each daughter cell receives identical genetic material. This separation occurs during anaphase when the centromere divides, allowing chromatids to move toward opposite poles of the cell.
Q2: When do sister chromatids separate during the cell cycle?
Sister chromatid separation occurs during anaphase, a stage of mitosis. At this point, the protein bonds holding sister chromatids together at the centromere break down. The separated chromatids, now individual chromosomes, move to opposite ends of the cell to be distributed to daughter cells.
Q3: What role does the centromere play in chromatid separation?
The centromere is the constricted region where sister chromatids attach before separation. It serves as the attachment point for spindle fibers that pull chromatids apart during anaphase. When the centromere divides, it signals the release of sister chromatids, allowing them to migrate to opposite poles.
Q4: How does chromosome segregation ensure genetic accuracy?
Chromosome segregation distributes identical sister chromatids equally to daughter cells, maintaining genetic consistency. Each daughter cell receives the same number and type of chromosomes as the parent cell. This precise separation prevents genetic imbalances and ensures proper cellular function in offspring cells.
Q5: What is the difference between sister chromatids and homologous chromosomes?
Sister chromatids are identical copies of a single chromosome joined at the centromere. Homologous chromosomes are different chromosome pairs, one from each parent, that separate during meiosis. Sister chromatids separate during mitosis, while homologous chromosomes separate during the first meiotic division.
Q6: What happens if sister chromatids fail to separate properly?
Failure of sister chromatids to separate, called nondisjunction, results in unequal chromosome distribution to daughter cells. Daughter cells may receive too many or too few chromosomes, causing aneuploidy. This chromosomal imbalance can lead to cell dysfunction, developmental abnormalities, or cell death.