Question

5A. (6pts) Please describe how microtubule dynamics play a role both in the assembly of the mitotic spindle during metaphase and the segregation of chromosomes during anaphase. B. (6pts) Nocodazole is a microtubule depolymerizing drug, and is often used to synchronize populations of cells so that they are in the same point in the cell cycle. Please describe how the molecular effect of nocodazole leads to cell synchronization. B. (6pts) You isolate mutant cells defective in the DNA-damage checkpoint, but you find that under normal laboratory conditions, the mutant cells grow and divide at the same rate as wild- type cells. Why doesn't the defect in the DNA-damage checkpoint have a large effect on cell growth and division rates under normal conditions?

Answer 1

5A) Microtubules are attached to chromosomes by kinetochores, which monitors spindle formation and prevent early anaphase onset. Microtubule polymerization and depolymerization dynamic drive chromosome congression. Depolymerization of microtubules generates tension at kinetochores. Bipolar attachment of sister kinetochores to microtubules emanating from opposite poles of the cell couples opposing tension forces, aligning chromosomes at the cell equator. Once every chromosome is bi-oriented, anaphase starts.

In Anaphase,the separation of the replicated chromosomes done by the mitotic spindle is formed from microtubules associated proteins (MAPs), which both pull the daughter chromosomes towards the poles of the spindle and move the poles apart.Both the assembly and the function of the mitotic spindle depend on microtubule-dependent motor proteins. Such proteins belong to 2 families—the kinesin-related proteins, which move toward the plus end of microtubules, and the dyneins, which move toward the minus end. In the mitotic spindle, the motor proteins operate at or near the ends of the microtubules. These ends are not only sites of microtubule assembly and disassembly, they are also sites of force production. The assembly and dynamics of the mitotic spindle rely on the shifting balance between opposing plus-end-directed and minus-end-directed motor proteins.