Daily Newsletter: October 30, 2013 - Somatic Nuclear Division

Daily Newsletter

October 23, 2012 - Somatic Nuclear Division

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Mitosis describes nuclear division of a somatic cell. We commonly use the term loosely to describe cell division, but that is an incorrect usage of the word mitosis. Cell division is better described by the term cytokinesis. It is important to use these terms correctly, as it will help you as you go further through biology.

Mitosis describes a nuclear division event, specifically in a somatic (as opposed to a sexual reproductive) cell. Most of the time we think of nuclear division occuring just prior to cytokinesis (cell division), but there are examples of cells that can undergo nuclear division without undergoing cytokinesis (coenocytic fungal cells have multiple nuclei enclosed by a single cellular membrane). For most eukaryotic cells though, mitosis will be followed by cytokinesis. Remember mitosis and cytokinesis are two different events.

Mitosis is also described as somatic nuclear division. The word somatic refers to general body cells. This is to contrast difference between a general cell and a reproductive cell. A reproductive cell, or gametic cell, will undergo a special type of nuclear division known as meiosis, which will be discussed in Thursdays's newsletter. Gametes are needed for sexual reproduction.

The goal of mitosis is to produce two daughter nuclei that are genetically identical. Coupling mitosis and cytokinesis results in the formation of two genetically identical daughter cells.

Prior to mitosis, DNA replication will have already occured. Every molecule of DNA will have undergone replication (DNA synthesis). We will discuss replication later this week.

The process of mitosis occurs in 4 Main Phases (there are additional phases that have been added in recent years). Below is a phrase to remember:

"Prophase sets up the process, metaphase aligns the chromosomes, anaphase seperates the chromosomes, and telophase returns the cell to normal."

These phrase describes the basic action of the four main steps: Prophase, Metaphase, Anaphase and Telophase.  In the past ten years, prometaphase has been included as a stage to help distinguish events that occur as the cell moves from prophase to metaphase.  You must remember that the stages are artificial attempts to describe a continuous process.  Once the M Phase begins (in this case mitosis), it does not stop until completion or the cell receives a signal for apoptosis.

[Review the University of Arazonia's Mitosis Tutorial. This will take you through the main phases, and includes the Prometaphase addition.]

In Prophase, we see the condensation (packaging) of the chromosomes. We also see the formation of the mitotic spindle. The image to the right shows Early and Late Prophase. In recent years, the term Late Prophase has been renamed as Prometaphase. This was done to indicate the rapid changes that being to take place within the cell, and to indicate the passing of a check point (NOTE: cells go through check (or restriction) points where signals will tell the cell to either proceed or abort the process of nuclear or cellular division. This restriction point deals with whether the mitotic spindle is correctly forming or not (if not, apoptosis).

In Prometaphase, microtubules of the mitotic spindle reach toward the centromere of each chromosome, forming the kinetochore. During this period, we will also see the dissolution of the nuclear envelope. The nuclear lamina (intermediate filaments) and nuclear pores begin to dissociate.

During Metaphase, the chromosomes are aligned down the imaginary equitorial line of the cell. This line is equidistant between the centrioles. The alignment is important. If you look at most drawings, the chromosomes are shown as aligning so that their centromeres are on the equitorial line, and individual chromatids are on either side of the line. This is to represent an equitorial division. As each sister chromatid of a chromosome represents a complete DNA molecule, the division of these will result in an equal number of chromosomes on either side of the equitorial line. So, a cell with 46 molecuels of DNA (chromosomes) will produce two dauther nuclei (and then cells) with 46 molecules of DNA (chromosomes). They will be genetically identical.

Beyond showing the arrangment of chromosomes, the image above also shows the different types of microtubules: Kinetochore, Polar and Aster. Aster, meaning star (Greek), comes from the starlike appearance of these microtubules. This starlike arrangment is also seen in the plant genus Aster, which is noted for the radial startlike flower petals. Note: they are sometimes referred to as Astral microtubules (Astral is an English adjetive derived from Aster).

Once the chromsomes have been arranged, they can be seperated. Anaphase is when there is visible seperation of the chromosomes into daughter chromatids. This link to an Anaphase Image is an excellent reference for what occurs in Anaphase (remember that you have motors that can move down microtubules). The image to the image to the right is a good quick visual of what starts to happen: the seperatation of chromatid. NOTE: At this point, there is no more chromosome; all we have left are the daughter chromatids. It is not uncommon though for people to start referring to these chomatids as chromosomes. As this can lead to a great deal of confusion, I want you to remember that at the end of anaphase we have daugter chromatids, not chromosomes.


During Telophase, the cell returns to normal interphase operation. The kinetochore microtubules will be released and begin to dissociate. The nuclear envelope will reform as the nuclear lamella (intermediate filaments) begin to reassociate. Once the protection of the nuclear envelope is reestablished, the DNA will be released from the supercoiled packing that produced the chromatids and chromosomes. As this process continues, cytokinesis can begin.
Remember, cytokinesis, or the division of the cell, does not have to take place after mitosis. For the vast majority of cells, mitosis and cytokinesis are coupled processes, but not all eukaryotes undergo cytokinesis. In animal cells, the act of cytokinesis is directed by the cytoskeleton, which causes the membrane to be pulled toward the center (remember the location of those polar microtubules?). As the membrane is dynamic, when pulled together, the phospholipid bilayers will "snap" together, or fuse, resulting in a seperation of the membranes.

Plants and fungi, which posses cell walls, experience cytokinesis in a dramatically different way. Prior to division, the plant cell will have made numerous vesicles that contain the raw materials needed to create cell walls. These materials are held in an inert state, with inactive enzymes needed to form these materials into walls. As telophase begins, these vesicles begin to line up down the equator of the cell, and begin to fuse (what do you think triggers this action? will it trigger the enzymes?). As the vesicles fuse, cell walls begin to form. As more vesicles fuse (remember the membrane is dynamic), the wall continues to grow (cell plate). Eventually the membrane surrounded wall will fuse with the parental cell wall. Once the cell plate fuses with the parental wall, you have two new daughter cells.
NOTE: Plant cell walls are generally impervious to water flow. As a by-product of plant cytokinesis, and the development of the cell plate, you will find holes between the two new daughter cells. Known as plasmodesmata, these membrane lined holes allow for a continuous cytoplasm between cells. This allows for rapid movement of water and nutrients (including plant hormones) between cells (Symplastic Flow).

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Study Note

You will notice that above I gave you a number of links. Do you think that they are important for your overall understanding of this topic?

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Remember This: The following phrase will help you as we move through genetics. Remember it!

"Base complementarity is the foundation of all genetic processes."

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Daily Challenge

Describe the process of mitosis in your own words. Feel free to use images, just reference where you got the image. Remember that this leads to your milestone paper and exam, spend some time to build a personal description of mitosis.

Daily Newsletter October 28, 2013 - The Cell Cycle

Daily Newsletter

October 28, 2013 - The Cell Cycle

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Reading:

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

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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 G₁ Phase, 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.

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".]

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.

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Daily Challenge

In your own words, describe the cell cycle. Then answer the following question: How are CDKs related to cancer?

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Optional Reading

If your really into the regulation of the cell cycle, try out this article:
Cyclins and Cell Cycle Regulation

Daily Newsletter: October 21, 2013 - DNA Replication

Daily Newsletter

October 21, 2013 - DNA Replication

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Textbooks have a tendency to make replication one of the most complext topics covered. With a tendency to throw all the current research and understanding at students, they rarely take a step back and try to explain it. This newsletters has two goals: 1) to help biology students understand DNA replication, and 2) to show you want is expected from a Biology Freshman/Sophmore.



Central Dogma of Biology

 Before we get into replication, let's take a step back and look at the three core genetic processes, a.k.a., the Central Dogma. The central dogma describes the flow of genetic information in a cell. The core idea is INFORMATION. You may recall some of our early discussion on DNA, and about base complimentarity and the directionality of the molecule. This will become important rather quickly, but for just this moment, I want you to concentrate on the fact that DNA carries information. Information on how to build RNA and Proteins, both of which will produce the phenotype (expression) of the cell. For this reason, DNA, RNA and Proteins are considered Informational Macromolecules. This means that the sequence of monomers contains infomation, e.g., instructions on how to build RNA and Proteins. Since it is critical, the sequence of nucleotides carries information.
As you can see from the diagram of central metabolism shown above, there are three processes: Replication, Transcription and Translation. Think about those words. They are words used in reference to languages and documents. When you replicate a docuement, you want to ensure that you are getting a faithful (or even exact) copy of the original.

When you transcribe, you are moving from one medium, e.g., spoken word, to another medium, e.g., text. If you watch news shows, they will tell you that transcripts of the show are available. Court reports make transcripts of the trial. You are taking the language from one medium (in our case DNA) to another medium (RNA). The language is still the same (i.e., nucleic acid lanugae), just in a different form. Does the transcript have to be 100% correct? You want it to be, but it is not as exacting as a replication.
Translation is where you change languages. Unless you're fluent in another language, you will need somoene to help translate, or at least a good translation dictionary. Now you are moving the context from one language (nucleic acid) to another language (amino acids).

All of these processes rely on one key feature of nucleic acids: BASE COMPLIMENTARITY. In DNA: A complements T, and G complements C. In RNA: U complements A, and G still complements C.

Replication

In replication our goal is to take one molecule of DNA and make two daughter molecules of DNA that are identical to the first. Even the best replication processes can produce errors, but our goal is to be error free. This takes precision! As DNA is long, we also need this to be a fast process.

The enzyme that is ultimately responsible for replication is DNA Polymerase. [NOTE: there are multiple types of DNA Polymerase, but for now you just need to understand the core concept common to the DNA Polymerase family.] DNA polymerase is only one component of the Replication Complex, which is a complex association of proteins needed to successfully complete the replication event. Your goal at this time is to concentrate on DNA polymerase; we will talk about some of the other components later.
DNA is a double stranded molecule, in which the strands are anti-parallel. This means that one strand starts at the 5' end → 3' end, while the the other strand is revered. This can be seen in the image to the right. A common way of saying this is that we read DNA in the 3' → 5' direction. Why is this important? DNA Polymerase can only read DNA in the 3' → 5' direction, and can only build a new strand in the 5' → 3' direction. Before we go on, let's look another time at how deoxyribonucleotides are polymerized.


To the left you will see a generic image showing DNA Polymerase adding nucleotides to a growing DNA strand. Look carefully: A deoxyribonucleotide triphosphate (dTTP) is being added. The 5' phosphate of the new nucleotide is what will be used to form the phosphodiester bond. DNA Polymerase requires a free 3' end on which to grow the new DNA strand. To the right is another image that will help you with this concept. At this point, the critical thing to remember is that DNA Polymerase will need a free 3' end on which to add a new nucleotide.
This requirement to build in only one direction (5' → 3') creates a problem for the DNA process: the two strands read in opposite directions, and each must be replicated. It was noticed that one strand appears to replicate continuously, while the opposite strand appears to replicate discontinuously.

The original strand that reads 5' → 3' can be used by DNA polymerase to continuously produce the new 5' → 3' strand (the antiparallel complement to the original strand). We refer to the continuous synthesis strand as the Leading Strand. The other original strand, which read 3' → 5' cannot be copied continuously. A section will have to be exposed, replicated, and then another section exposed. This strand is constructed discontinuously, and is reffered to as the Lagging Strand.The image above shows the leading and lagging strand. Notice that the leading strand is replicating toward the Replication Fork(where the original strands seperate). As more DNA unwinds and opens, DNA synthesis continues down the leading strand.
The lagging strand though has to build in a start-stop action, producing Okazaki fragments. These fragments have to be sealed (phosphodiester bonds) together before DNA can rewind into the α-helix.

In the image above, you will notice a number of enzymes on the lagging strand. These enzymes are required for the initiation of DNA polymerazation, and then sealing the fragments. Looking at the image, you will see an enzyme called Primase, and a structure in red known as a Primer. Another restriction on DNA polymerase is that it must have a free 3' end from which to start building. DNA Polymerase is prevented from building a DNA strand from nothing. Something (a primer) must be in place upon which DNA polymerase can build. The Primer is constructed from RNA, and is a temporary scaffold upon which DNA polymerase can start working.

Eventually the primer will need to be moved. This is where you need to learn a little more about DNA polymerase. There are multiple DNA polymerases in eukaryotic systems. The general work horse of replication is DNA Polymerase III (DNA pol III), which is used to make long strands of DNA. DNA Polymerase I (DNA pol I) is used to replace primers (it is also used in repair functions). Even after the RNA primer is replaced with DNA, there is still a gap between fragments. Ligase is the enzyme used to create a phosphodiester bond between fragments, thus sealing the new sugar-phosphate backbone of the synthesized strand.

The result of DNA replication is that one molecule one DNA was used to create two new molecules of DNA. The two strands of the original DNA molecule became the template from which to build new complimentary strands of DNA. This is referred to as semi-conservative replication, as each new molecule has one strand from the original molecule, and one freshly synthesized complimentary strand.

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Daily Challenge

In your own words describe the purpose and process of replication.

Special Edition: October 25, 2012 - DNA Replication

Special Edition

October 25, 2012 DNA Replication

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Textbooks have a tendency to make replication one of the most complext topics covered. With a tendency to throw all the current research and understanding at students, they rarely take a step back and try to explain it. This newsletters has two goals: 1) to help biology students understand DNA replication, and 2) to show you want is expected from a Biology Freshman/Sophmore.



Central Dogma of Biology

 Before we get into replication, let's take a step back and look at the three core genetic processes, a.k.a., the Central Dogma. The central dogma describes the flow of genetic information in a cell. The core idea is INFORMATION. You may recall some of our early discussion on DNA, and about base complimentarity and the directionality of the molecule. This will become important rather quickly, but for just this moment, I want you to concentrate on the fact that DNA carries information. Information on how to build RNA and Proteins, both of which will produce the phenotype (expression) of the cell. For this reason, DNA, RNA and Proteins are considered Informational Macromolecules. This means that the sequence of monomers contains infomation, e.g., instructions on how to build RNA and Proteins. Since it is critical, the sequence of nucleotides carries information.
As you can see from the diagram of central metabolism shown above, there are three processes: Replication, Transcription and Translation. Think about those words. They are words used in reference to languages and documents. When you replicate a docuement, you want to ensure that you are getting a faithful (or even exact) copy of the original.

When you transcribe, you are moving from one medium, e.g., spoken word, to another medium, e.g., text. If you watch news shows, they will tell you that transcripts of the show are available. Court reports make transcripts of the trial. You are taking the language from one medium (in our case DNA) to another medium (RNA). The language is still the same (i.e., nucleic acid lanugae), just in a different form. Does the transcript have to be 100% correct? You want it to be, but it is not as exacting as a replication.
Translation is where you change languages. Unless you're fluent in another language, you will need somoene to help translate, or at least a good translation dictionary. Now you are moving the context from one language (nucleic acid) to another language (amino acids).

All of these processes rely on one key feature of nucleic acids: BASE COMPLIMENTARITY. In DNA: A complements T, and G complements C. In RNA: U complements A, and G still complements C.

Replication

In replication our goal is to take one molecule of DNA and make two daughter molecules of DNA that are identical to the first. Even the best replication processes can produce errors, but our goal is to be error free. This takes precision! As DNA is long, we also need this to be a fast process.

The enzyme that is ultimately responsible for replication is DNA Polymerase. [NOTE: there are multiple types of DNA Polymerase, but for now you just need to understand the core concept common to the DNA Polymerase family.] DNA polymerase is only one component of the Replication Complex, which is a complex association of proteins needed to successfully complete the replication event. Your goal at this time is to concentrate on DNA polymerase; we will talk about some of the other components later.
DNA is a double stranded molecule, in which the strands are anti-parallel. This means that one strand starts at the 5' end → 3' end, while the the other strand is revered. This can be seen in the image to the right. A common way of saying this is that we read DNA in the 5' → 3' direction. Why is this important? DNA Polymerase can only read DNA in the 5' → 3' direction, and can only build a new strand in the 3' → 5' direction. Before we go on, let's look another time at how deoxyribonucleotides are polymerized.


To the left you will see a generic image showing DNA Polymerase adding nucleotides to a growing DNA strand. Look carefully: A deoxyribonucleotide triphosphate (dTTP) is being added. The 5' phosphate of the new nucleotide is what will be used to form the phosphodiester bond. DNA Polymerase requires a free 3' end on which to grow the new DNA strand. To the right is another image that will help you with this concept. At this point, the critical thing to remember is that DNA Polymerase will need a free 3' end on which to add a new nucleotide.
This requirement to build in only one direction (3' → 5') creates a problem for the DNA process: the two strands read in opposite directions, and each must be replicated. It was noticed that one strand appears to replicate continuously, while the opposite strand appears to replicate discontinuously.

The original strand that reads 5' → 3' can be used by DNA polymerase to continuously produce the new 3' → 5' strand (the antiparallel complement to the original strand). We refer to the continuous synthesis strand as the Leading Strand. The other original strand, which read 3' → 5' cannot be copied continuously. A section will have to be exposed, replicated, and then another section exposed. This strand is constructed discontinuously, and is reffered to as the Lagging Strand.The image above shows the leading and lagging strand. Notice that the leading strand is replicating toward the Replication Fork(where the original strands seperate). As more DNA unwinds and opens, DNA synthesis continues down the leading strand.
The lagging strand though has to build in a start-stop action, producing Okazaki fragments. These fragments have to be sealed (phosphodiester bonds) together before DNA can rewind into the α-helix.

In the image above, you will notice a number of enzymes on the lagging strand. These enzymes are required for the initiation of DNA polymerazation, and then sealing the fragments. Looking at the image, you will see an enzyme called Primase, and a structure in red known as a Primer. Another restriction on DNA polymerase is that it must have a free 3' end from which to start building. DNA Polymerase is prevented from building a DNA strand from nothing. Something (a primer) must be in place upon which DNA polymerase can build. The Primer is constructed from RNA, and is a temporary scaffold upon which DNA polymerase can start working.

Eventually the primer will need to be moved. This is where you need to learn a little more about DNA polymerase. There are multiple DNA polymerases in eukaryotic systems. The general work horse of replication is DNA Polymerase III (DNA pol III), which is used to make long strands of DNA. DNA Polymerase I (DNA pol I) is used to replace primers (it is also used in repair functions). Even after the RNA primer is replaced with DNA, there is still a gap between fragments. Ligase is the enzyme used to create a phosphodiester bond between fragments, thus sealing the new sugar-phosphate backbone of the synthesized strand.

The result of DNA replication is that one molecule one DNA was used to create two new molecules of DNA. The two strands of the original DNA molecule became the template from which to build new complimentary strands of DNA. This is referred to as semi-conservative replication, as each new molecule has one strand from the original molecule, and one freshly synthesized complimentary strand.

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Optional Challenge

In your own words describe the purpose and process of replication. While you are encouraged to deepen your knowledge of replication, you are only required at this time to go into as much detail as was presented in this newsletter.
Link to Forum

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Link to Lecture Reflection Forum

Daily Newsletter: October 24, 2012 - The Cell Cycle

Daily Newsletter

October 24, 2012 The Cell Cycle

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Reading:

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

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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 G₁ Phase, 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.

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".]

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.

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Daily Challenge

In your own words, describe the cell cycle. Then answer the following question: How are CDKs related to cancer?
Link to Forum

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Optional Reading

If your really into the regulation of the cell cycle, try out this article:
Cyclins and Cell Cycle Regulation

Daily Newsletter: October 23, 2012 - Nuclear Division

Daily Newsletter

October 23, 2012 Nuclear Division

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Mitosis describes nuclear division. We commonly use the term loosely to describe cell division, but that is an incorrect usage of the word mitosis. Cell division is better described by the term cytokinesis. It is important to use these terms correctly, as it will help you as you go further through biology.

Mitosis describes a nuclear division event. Most of the time we think of nuclear division occuring just prior to cytokinesis (cell division), but there are examples of cells that can undergo nuclear division without undergoing cytokinesis (many fungi do this). For most eukaryotic cells though, mitosis will be followed by cytokinesis. Remember though that these are two different events.

Mitosis is also described as somatic nuclear division. The word somatic refers to general body cells. This is to contrast difference between a general cell and a reproductive cell. A reproductive cell, or gametic cell, will undergo a special type of nuclear division known as meiosis, which will be discussed in Thursday's newsletter. Gametes are needed for sexual reproduction.

The goal of mitosis is to produce two daughter nuclei that are genetically identical. Coupling mitosis and cytokinesis results in the formation of two genetically identical daughter cells.

Prior to mitosis, DNA replication will have already occured. Every molecule of DNA will have undergone replication (DNA synthesis). We will discuss replication later this week.

The process of mitosis occurs in 4 Main Phases (there are additional phases that have been added in recent years). Below is a phrase to remember:

"Prophase sets up the process, metaphase aligns the chromosomes, anaphase seperates the chromosomes, and telophase returns the cell to normal."

These phrase describes the basic action of the four main steps: Prophase, Metaphase, Anaphase and Telophase.

[Review the University of Arazonia's Mitosis Tutorial. This will take you through the main phases, and includes the Prometaphase addition.]

In Prophase, we see the condensation of the chromosomes, which were discussed in yesterday's newsletter. We also see the formation of the mitotic spindle. The image to the right shows Early and Late Prophase. In recent years, the term Late Prophase has been renamed as Prometaphase. This was done to indicate the rapid changes that being to take place within the cell, and to indicate the passing of a check point (NOTE: cells go through check (or restriction) points where signals will tell the cell to either proceed or abort the process of nuclear or cellular division.

In Prometaphase, microtubules of the mitotic spindle reach toward the centromere of each chromosome, forming the kinetochore. During this period, we will also see the dissolution of the nuclear envelope. The nuclear lamella (intermediate filaments) begin to dissociate. As they do, the phospholipids of the nuclear membrane wrap around them forming submicroscopic vesicles (i.e.,can not be see under a light microscope).

During Metaphase, the chromosomes are aligned down the imaginary equitorial line of the cell. This line is equidistant between the centrioles. The alignment is important. If you look at most drawings, the chromosomes are shown as aligning so that their centromeres are on the equitorial line, and individual chromatids are on either side of the line. This is to represent an equitorial division. As each sister chromatid of a chromosome represents a complete DNA molecule, the division of these will result in an equal number of chromosomes on either side of the equitorial line. So, a cell with 46 molecuels of DNA (chromosomes) will produce two dauther nuclei (and then cells) with 46 molecules of DNA (chromosomes). They will be genetically identical.

Beyond showing the arrangment of chromosomes, the image above also shows the different types of microtubules: Kinetochore, Polar and Aster. Aster, meaning star (Greek), comes from the starlike appearance of these microtubules. This starlike arrangment is also seen in the plant genus Aster, which is noted for the radial startlike flower petals. Note: they are sometimes referred to as Astral microtubules (Astral is an English adjetive derived from Aster).

Once the chromsomes have been arranged, they can be seperated. Anaphase is when there is visible seperation of the chromosomes into daughter chromatids. This link to an Anaphase Image is an excellent reference for what occurs in Anaphase (remember that you have motors that can move down microtubules). The image to the image to the right is a good quick visual of what starts to happen: the seperatation of chromatid. NOTE: At this point, there is no more chromosome; all we have left are the daughter chromatids. It is not uncommon though for people to start referring to these chomatids as chromosomes. As this can lead to a great deal of confusion, I want you to remember that at the end of anaphase we have daugter chromatids, not chromosomes.

During Telophase, the cell returns to normal interphase operation. The kinetochore microtubules will be released and begin to dissociate. The nuclear envelope will reform as the nuclear lamella (intermediate filaments) begin to reassociate. Once the protection of the nuclear envelope is reestablished, the DNA will be released from the supercoiled packing that produced the chromatids and chromosomes. As this process continues, cytokinesis can begin.
Remember, cytokinesis, or the division of the cell, does not have to take place after mitosis. For the vast majority of cells, mitosis and cytokinesis are coupled processes, but not all eukaryotes undergo cytokinesis. In animal cells, the act of cytokinesis is directed by the cytoskeleton, which causes the membrane to be pulled toward the center (remember the location of those polar microtubules?). As the membrane is dynamic, when pulled together, the phospholipid bilayers will "snap" together, or fuse, resulting in a seperation of the membranes.
Plants and fungi, which posses cell walls, experience cytokinesis in a dramatically different way. Prior to division, the plant cell will have made numerous vesicles that contain the raw materials needed to create cell walls. These materials are held in an inert state, with inactive enzymes needed to form these materials into walls. As telophase begins, these vesicles begin to line up down the equator of the cell, and begin to fuse (what do you think triggers this action? will it trigger the enzymes?). As the vesicles fuse, cell walls begin to form. As more vesicles fuse (remember the membrane is dynamic), the wall continues to grow (cell plate). Eventually the membrane surrounded wall will fuse with the parental cell wall. Once the cell plate fuses with the parental wall, you have two new daughter cells.
NOTE: Plant cell walls are generally impervious to water flow. As a by-product of plant cytokinesis, and the development of the cell plate, you will find holes between the two new daughter cells. Known as plasmodesmata, these membrane lined holes allow for a continuous cytoplasm between cells. This allows for rapid movement of water and nutrients (including plant hormones) between cells (Symplastic Flow).

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Study Note

You will notice that above I gave you a number of links. Do you think that they are important for your overall understanding of this topic?

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Remember This: The following phrase will help you as we move through genetics. Remember it!

"Base complementarity is the foundation of all genetic processes."

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Daily Challenge

Describe the process of mitosis in your own words. Feel free to use images, just reference where you got the image. Remember that this leads to your milestone paper and exam, spend some time to build a personal description of mitosis.
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