Prophase and Prometaphase
As we discussed in cell cycle, before cells are allowed to enter M phase they must meet certain cellular requirements. Among these requirements are appropriate cell size and cellular environment. Following DNA replication in S phase, cells contain twice their normal number of chromosomes. Because cells that undergo mitosis are diploid, their number of chromosomes can be represented as 2N, where N equals the number of distinct chromosomes in the cell. Cells about to enter M phase, which have passed through S phase and replicated their DNA, have 4N chromosomes. Entry into M phase is allowed by the formation of the mitotic cyclin-Cdk complex known as M phase-promoting factor that occurs as a cell cycle regulatory mechanism in the G2 phase.
The first phase of mitosis within M phase is called prophase. It follows G2, the final phase of interphase. A cell entering M phase manifests a number of physicsl signs. Among these are condensation, or thickening, of chromosomes. Chromosome condensation is visible through a microscope and is required for subsequent chromosome separation during later stages of mitosis. Another physical characteristic of cells beginning mitosis is the sprouting of microtubules from replicated centrosomes. Microtubles are protein filaments on which chromosomes migrate during mitosis.
As we discussed, prophase is marked by very thick and dense chromosomes. At this phase, the chromosomes are still enclosed in the cell nucleus within the nuclear envelope. The chromosomes also contain a centromere, which is necessary in later phases for attachment to microtubules for migration. Late in prophase, kinetochores assemble on the centromeres. Specialized microtubules, called kinetochore microtubules later attach to these sites. Duplicated centrosomes, which are the organizing centers of microtubules, begin to separate towards opposite poles of the cell. The network of cytoskeletal components begins to break down and the mitotic spindle forms. The mitotic spindle is an arrangement of microtubules that is responsible for aligning duplicated chromosomes in later phases.
The major event marking a cell's entry to prometaphase is the breakdown of the nuclear envelope into small vesicles. Kinetochores also become fully matured on the centromeres of the chromosomes. The disruption of the nuclear envelope allows for the mitotic spindles to gain access to the mature kinetochores. As the microtubles of the mitotic spindle enter the nuclear region, some attach to the kinetochores making them kinetochore microtubules. The remaining microtubules are called non-kinetochore microtubules. Sister chromatids are captured by microtubules stemming from centrosomes on opposite ends of the cell. Once they have captured chromosomes, the kinetochore mictrotubles begin to exert force on the chromosomes, moving them.