Question

A. Provide an overview of the eukaryotic cell cycle, including cellular activities during different phases of the cycle.

B. Explain how the cell cycle is cyclically controlled, including the roles of cyclins and cyclin- dependent kinases (Cdks).

C. Describe the activities of the chromosomes and cytoskeleton during M-phase of the cell cycle.

Answer 1

A. The division cycle of most cells consists of four coordinated processes: cell growth, DNAreplication, distribution of the duplicated chromosomes to daughter cells, and cell division. In bacteria, cell growth and DNA replication take place throughout most of the cell cycle, and duplicated chromosomes are distributed to daughter cells in association with the plasma membrane. In eukaryotes, however, the cell cycle is more complex and consists of four discrete phases. Although cell growth is usually a continuous process, DNA is synthesized during only one phase of the cell cycle, and the replicated chromosomes are then distributed to daughter nuclei by a complex series of events preceding cell division. Progression between these stages of the cell cycle is controlled by a conserved regulatory apparatus, which not only coordinates the different events of the cell cycle but also links the cell cycle with extracellular signals that control cell proliferation.

A typical eukaryotic cell cycle is illustrated by human cells in culture, which divide approximately every 24 hours. As viewed in the microscope, the cell cycle is divided into two basic parts: mitosis and interphase. Mitosis (nuclear division) is the most dramatic stage of the cell cycle, corresponding to the separation of daughter chromosomes and usually ending with cell division (cytokinesis). However, mitosis and cytokinesis last only about an hour, so approximately 95% of the cell cycle is spent in interphase—the period between mitoses. During interphase, the chromosomes are decondensed and distributed throughout the nucleus, so the nucleus appears morphologically uniform. At the molecular level, however, interphase is the time during which both cell growth and DNA replication occur in an orderly manner in preparation for cell division.

The cell grows at a steady rate throughout interphase, with most dividing cells doubling in size between one mitosis and the next. In contrast, DNA is synthesized during only a portion of interphase. The timing of DNA synthesis thus divides the cycle of eukaryotic cells into four discrete phases.

The M phase of the cycle corresponds to mitosis, which is usually followed by cytokinesis. This phase is followed by the G1 phase (gap 1), which corresponds to the interval (gap) between mitosis and initiation of DNA replication. During G1, the cell is metabolically active and continuously grows but does not replicate its DNA. G1 is followed by S phase (synthesis), during which DNA replication takes place. The completion of DNA synthesis is followed by the G2 phase (gap 2), during which cell growth continues and proteins are synthesized in preparation for mitosis.

B. Cyclins are among the most important core cell cycle regulators. Cyclins are a group of related proteins, and there are four basic types found in humans and most other eukaryotes:As the names suggest, each cyclin is associated with a particular phase, transition, or set of phases in the cell cycle and helps drive the events of that phase or period. For instance, M cyclin promotes the events of M phase, such as nuclear envelope breakdown and chromosome condensation. The levels of the different cyclins vary considerably across the cell cycle, as shown in the diagram at right. A typical cyclin is present at low levels for most of the cycle, but increases strongly at the stage where it's needed.

Cyclins drive the events of the cell cycle by partnering with a family of enzymes called the cyclin-dependent kinases(Cdks). A lone Cdk is inactive, but the binding of a cyclin activates it, making it a functional enzyme and allowing it to modify target proteins. Cdks are kinases, enzymes that phosphorylate (attach phosphate groups to) specific target proteins. The attached phosphate group acts like a switch, making the target protein more or less active. When a cyclin attaches to a Cdk, it has two important effects: it activates the Cdk as a kinase, but it also directs the Cdk to a specific set of target proteins, ones appropriate to the cell cycle period controlled by the cyclin.

Cdk levels remain relatively constant across the cell cycle, but Cdk activity and target proteins change as levels of the various cyclins rise and fall. In addition to needing a cyclin partner, Cdks must also be phosphorylated on a particular site in order to be active (not shown in the diagrams in this article), and may also be negatively regulated by phosphorylation of other site