DNA Part III: The Cell Cycle “The Life of a Cell”

2 Cells must reproduce else they die. The "life of a cell" is termed the cell cycle. The cell cycle has distinct phases, which are called G 1, S, G 2, and M. Cells that have temporarily or reversibly stopped dividing are said to have entered a state of quiescence called G 0 phase. Cells & Cell Reproduction

3 During this time organelles are reproducing, protein synthesis is occurring for growth and differentiation. Because, transcription is occurring, the DNA is uncoiled. This phase is the most variable, ranging from almost nothing to years. The G 1 Phase of the Cell Cycle

4 The average time for G 1 is around 10 hours if the cell cycle lasts 24 hours. Most cells that differentiate will do so during this phase. Cells arrested in G 1 may no longer have the capability of reproducing and are said to be in G 0. Certain cells in G 0, however, when given some external or internal cues may revert back to G 1 and enter the cell cycle again. Nerve and muscle cells are usually arrested in G 0.

5 The S or synthesis phase is the second phase of the cell cycle. DNA uncoils DNA replication occurs Additional organelle replication occurs This phase ensures that each emerging daughter cell will have the same genetic content as the mother cell. S Phase of the Cell Cycle

6 The G 2 or Gap 2 phase occupies the time from the end of S until the onset of mitosis. During this time, the cell prepares for mitosis by making and organizing necessary proteins such as the tubulin needed to construct microtubules which used to make spindle fibers. G 2 Phase of the Cell Cycle

During mitosis the nucleus is replicated and the cytoplasm divides to produce two genetically identical daughter cells. The phases are triggered by the accumulation of cell signals. M Phase or Mitosis

8 This graph represents the amount of DNA found in the cell during the cell cycle. The Amount of DNA Varies During the Cell Cycle

9 The control of the cell cycle is dependent on an accumulation of “signal molecules”. Quite often these signal molecules must be phosphorylated in order to be functional. This are simple illustrations. Internal Controls of the Cell Cycle

Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes. A kinase is a type of enzyme that transfers phosphate groups from high- energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. 10 Cyclins vs. Kinases

11 Cyclins vs. Kinases Certain cyclins are made at certain times during the cell cycle, and their concentration will rise and fall. Cyclins are also destroyed after they are no longer needed by the cell. CDKs are not destroyed as they are only activated or deactivated.

12 Certain kinases may have two forms (active and inactive). Kinases are enzymes (proteins) that phosphorylate certain molecules or other enzymes. Most cell cycle signals are phosphorylated by kinases. Kinases Phosphorylate Cell Signal Molecules

13 Cyclins Activate Kinases Most cell cycle kinases are activated by molecules called cyclins. A kinase that requires a cyclin for activation is called a cyclin-dependent kinase or CDK.

14 Cyclins Activate Kinases Once the CDK phosphory- lates certain signals, the cyclin is destroyed. In the cell, the concentration of cyclins will rise and fall depending on the phase of the cell cycle. When the cyclin is destroyed the CDK returns to an inactive form.

15 Cyclins Activate Kinases Above is an example of how the M cyclin concentration affects MPF or M/CDK activity.

16 Cyclic Nature of Cyclins in the Cell Cycle This graph displays the cyclic nature of various cyclins in a given cell cycle

17 Different Types of Cyclins These are some known cyclin/CDK complexes and their role in the cell cycle. Cyclin/CDK Complex CyclinFunction of Cyclin/CDK Complex G1-CDKCyclin D Drives the transition G 1  S transition G1/S-CDKCyclin ECyclins bind to CDK at the end of G 1 and commits the cell to DNA replication. S-CDKCyclin ACyclins bind the CDK during S and are necessary for the initiation of DNA replication M-CDKCyclin BCyclins promote the events of Mitosis

18 Cyclins/CDKs Control the Cell Cycle

19 External Factors Also Influence the Cell Cycle Cell reproduction and the healing of a wound. I. Hemostasis II. Inflammation III. Proliferation IV. Remodeling