At the end of S phase, the immensely long DNA molecules of the sister chromatids are tangled in a mass of partially catenated DNA and proteins. Any attempt to pull the sisters apart in this state would undoubtedly lead to breaks in the chromosomes. To avoid this disaster, the cell devotes a great deal of energy in early mitosis to gradually reorganizing the sister chromatids into relatively short, distinct structures that can be pulled apart more easily in anaphase. These chromosomal changes involve two processes: chromosome condensation, in which the chromatids are dramatically compacted; and sister-chromatid resolution, whereby the two sisters are resolved into distinct, separable units (Figure 17–21). Resolution results from the decatenation of the sister DNAs, accompanied by the partial removal of cohesin molecules along the chromosome arms. As a result, when the cell reaches metaphase, the sister chromatids appear in the microscope as compact, rodlike structures that are joined tightly at their centromeric regions and only loosely along their arms.
Figure 17–20 The activation of M-Cdk.
Cdk1 associates with m-cyclin as the levels of m-cyclin gradually rise. The resulting m-Cdk complex is phosphorylated on an activating site by the Cdk-activating kinase (Cak) and on a pair of inhibitory sites by the Wee1 kinase. The resulting inactive m-Cdk complex is then activated at the end of g2 by the phosphatase Cdc25. Cdc25 is further stimulated by active m-Cdk, resulting in positive feedback. This feedback is enhanced by the ability of m-Cdk to inhibit Wee1.
Figure 17–21 The mitotic chromosome.
scanning electron micrograph of a human mitotic chromosome, consisting of two sister chromatids joined along their length. The constricted regions are the centromeres. (Courtesy of Terry d. allen.)
PROPHASE1centrosome forming mitotic spindle condensing replicated chromosome, consisting of two sister chromatids held together along their length intact nuclear envelope kinetochore At prophase, the replicated chromosomes, each consisting of two closely associated sister chromatids, condense. Outside the nucleus, the mitotic spindle assembles between the two centrosomes, which have replicated and moved apart. For simplicity, only three chromosomes are shown. In diploid cells, there would be two copies of each chromo-some present. In the fuorescence micrograph, chromosomes are stained orange and microtubules are green.PROMETAPHASE 2 Prometaphase starts abruptly with the breakdown of the nuclear envelope. Chromosomes can now attach to spindle microtubules via their kinetochores and undergo active movement. centrosome at spindle pole kinetochore microtubule chromosome in active motion fragments of nuclear envelope METAPHASE 3 At metaphase, the chromosomes are aligned at the equator of the spindle, midway between the spindle poles. The kinetochore microtubules attach sister chromatids to opposite poles of the spindle. centrosome at spindle pole kinetochore microtubule PANeL 17–1: The Principle Stages of M Phase (Mitosis and Cytokinesis) in an Animal Cell 980