Daily Newsletter

October 24, 2012 The Cell Cycle

Reading:

The Eukaryotic Cell Cycle
This is an excellent overview of the cell cycle. This is considered supplemental to what is in your textbook.

The cell cycle describes the life stages of a cell. It starts just after cytokinesis, and continues until the next cytokinetic (or mitotic) event. The period when a cell is growing between division events is known as interphase.

Interphase is divided into three distinct steps: G₁ Phase, S Phase, and G₂ Phase.

The G₁ Phase stands for Gap 1 Phase, and begins just after cytokinesis. Gap refers to no visible change in the cell. Another good term for G is growth, and that is usually what happens during this phase. The cell is building primary products, compounds such as amino acids, phospholipids, carbohydrates, triglycerides. These are describe as primary products as they are the cellular biochemicals needed to increase the cells size (biomass). Thus we generally consider the G₁ phase as the timethe cell increases in size. Another way to say this is that a major goal in this phase is the development of biomass.
[NOTE: In multicellular organisms, some cells will stop mitosis. They are locked in what is known as the G₀ phase. The G₀ phase is similar to the G₁Phase, but the cell will never level leave this physiological stage. After reading this newletter, I want you to consider a question: Why would you stop in the G₀ Phase if you were never going to replicate again?]

When the cell gets a signal to divide, the physiology of the cell changes. Metabolic pathways for creating deoxyribonucleotides are unlocked (dATP, dTTP, dGTP, dCTP). The cell will use these deoxyribonucleotides to synthesize DNA (Replication). The production of enzymes needed to replicate DNA will also be begin. (Think back to cell signaling).

During the S Phase, cellular metabolism is focused on DNA replication (S stands for DNA Synthesis). This is a complex event, takes time, and has consequences if there is an error; so most of the cell's work is dealing with DNA replication.

Once S Phase has begun, the cell has committed its self to the process of Nuclear Division and Cytokinesis. You never replicate DNA without moving toward Nuclear division, DNA replication without nuclear division usually results in cell termination.

After DNA replication, the cell needs to build all of the proteins and compounds used during Nuclear Division and Cytokinesis. This is the goal of the G₂ Phase. The G₂ Phase will continue until the required components are constructed, and the cell receives the signal to continue. At this point the cell moves into the M phase (which stands for either mitosis or meiosis).

Regulation

The processes of the cell cycle is tightly regulated.
What happens in unregulated or uncontrolled cell growth?

The regulation is based on Signals (yes, we're back to signals). To maintain homeostasis, an organism must replace certain cells during its life time. For instance, humans replace skin and mucous membranes constantly. Hormones, such as insulin-like growth factors, are signals used to make sure the body maintains its self by replacing cells.
CDK

Inside of cells, there is an internal signal system based on the protein family Cyclin Depdendent Kinases (CDK). Note, this is a family of proteins involved in cell cycle regulation (they also have a few other functions). As the name implies, the protein needs a Cyclin to function. For example, CDK2 requires Cyclin E during G₁. (NOTE: Cyclinn is a family of protein signal molecules assoiated with the cell cycle).

CDKs are always produced in mitotically active cells. (What term do we use for a protein that is always produced?)
Cells don't always have Cyclin, but instead produce them in response to a signal. [Note: The signals differ depending on if you are dealing with multicellular, colonial or singal celled eukaryotes, so we are not going to get into specifics. As these control vital processes that could cause damage to cells, e.g., think cancer, they have a very complex signal transduction. Think of it this way, the cell has to have get numerous "permissions" before it starts producing Cyclin, so it is highly regulated. For the purpose of this class, we will just say that it is controlled by "Growth Factors".]

CDK Check Points

Throughout the cell cycle, there are time points referred to as Check Points. These check points are where regulation occurs. For example, to move from the G₁ Phase to the S phase, you need to produce a set of cyclins to induce the activity of CDKs. The Cyclin-CDK complexes can then phosphorylate proteins. Why would you need to phosphorylate proteins?

During the G₁ Phase, the check point determines if you turn on the production of deoxyribonucleotides and the production of replication complex enzymes. There are check points in the G₁ Phase, S Phase, G₂ Phase, and M Phase. Many of these check points are determinations of the health of the cell, or the correctness of DNA replication and chromosome condensation. The image to the right shows the major check points, as well as the cyclin needed to activate (Cyc D to make deoxyribonucleic acids and the replication complex, Cyce to start the S phase, Cyc A to make sure replication is occuring properly, Cyc B to make sure the cell is ready for mitosis). Note: the check point in mitosis (M phase) is not shown. The M phase check point is to ensure that chromosomes have properly condensed and migrated.
As you can tell, the check points are there to make sure that the process is occuring properly. Consider the Cyclin/CDK system as the Quality Assurance & Quality Control (QA/QC) officer of the cell.

G_o Phase (in case you missed it the first time around)
Some cells become non-mitotic at a given point in development. For example, nerve cells stop dividing, as do cardiac muscle cells. When a cell becomes non-mitotic, it shifts from the G₁ Phase to the G_o Phase. The cell can be locked from mitosis by blocking the genes for either CDK or Cyclin.