Chromosomes and the Cell Cycle

You are made of many different types of cells. Nerve cells, skin cells, muscle cells, and many more. These cells obviously have many different functions, yet they all develop from the first cell that makes you. So do they all have the same DNA? Are all the cells in your body genetically identical? How does the first cell of an organism know to become two cells, then four cells, and so on? What tells these cells what to do? Your body produces about 25 million genetically identical cells every second. These new cells are formed when older cells divide, a process called cell division or cell reproduction. Cell division is the final step in the life of a cell, otherwise known as the cell cycle. Eukaryotic cells and prokaryotic cells complete this process by a number of different mechanisms. The cell cycle is a repeating series of events, during which the eukaryotic cell carries out its necessary functions, including metabolism, cellular growth, and division, resulting in two genetically identical daughter cells. To produce two genetically identical daughter cells, the chromosomes need to replicate and the nucleus and cytoplasm need to divide. These are key events in the life of a cell.

Cell Division in Prokaryotes

Prokaryotic organisms reproduce asexually by binary fission, a process that produces identical offspring (Figure 1). In asexual reproduction, a single parent produces genetically identical offspring. As prokaryotes do not have a nucleus, and have only one circular chromosome, they do not need to reproduce by the same mechanism as eukaryotic cells. Prokaryotic cell division is a much simpler process. In prokaryotic cell division, after the single chromosome is copied, the cell grows larger. Eventually the two chromosomes separate and move to opposite ends of the cell. Newly formed cell membrane then grows into the center of the cell, separating the two chromosomes, and forming two genetically identical daughter cells. The formation of two daughter cells is called cytokinesis. Under ideal conditions, reproduction in bacteria is extremely efficient, with some bacteria reproducing every 20 minutes. This makes bacteria an extremely effective tool for the molecular biologist. However, bacteria do not usually live in ideal conditions; otherwise, bacteria would grow and divide extremely rapidly, eventually covering the surface of Earth. Bacterial growth is limited by nutrients and water, predation, and by their own wastes.

Cell Division in Eukaryotes

Cell division in eukaryotic organisms is very different from that in prokaryotes, mainly because of the many chromosomes in the nuclei of eukaryotic cells. Cell division in eukaryotic organisms is necessary for development, growth, and repair. This cell division ensures that each resulting daughter cell receives a complete copy of the organism’s entire genome. Remember that all of an organism’s DNA must be present in each somatic, or body, cell. This DNA contains the information necessary for that cell to perform its functions, and to give that organism its traits. Therefore, prior to cell division, the eukaryotic cell’s complete genome must be copied, ensuring that each daughter cell receives a complete set of the genome.

The formation of gametes, an organism’s reproductive cells, such as sperm and egg cells, involves a completely different method of cell division. This cell division ensures that each gamete receives half the amount of an organism’s DNA.

 

 

Figure 1: Binary fission. In binary fission, the single chromosome is copied and eventually separates into two separate chromosomes, the cell grows larger, and two identical cells form by cytokinesis.

DNA, Chromosomes, and Genes

DNA contains the information necessary to make proteins, direct a cell’s activities, and give an organism its traits. This information is organized into structural units scattered along the length of the DNA molecule. These units are known as genes. A gene contains the information necessary to encode an RNA molecule or a protein. A single DNA molecule contains hundreds to thousands of genes. Different cell types use the information in different genes to make different proteins. This process gives different cell types distinct activities. Thus, a liver cell will have many different proteins than a kidney cell, giving the two cells types distinct activities. When a cell is using the information within a gene, the segment of DNA containing that gene is unwound, exposing the double helix to the cell machinery needed to use that information.

Prior to cell division, the DNA must duplicate itself in a process called DNA replication. This ensures that each resulting cell receives a complete set of the organism’s genome. But how is the replicated DNA divided up evenly? What guarantees that each new cell will receive a complete set of DNA? It was the identification of chromosomes that allowed this process to be characterized. As a eukaryotic cell prepares to divide, the DNA and associated proteins (histones) coil into a structure, known as a chromosome (Figure 2). The DNA copies itself prior to this process, so the chromosome that forms consists of two identical chromatids, known as sister chromatids, identical copies of DNA. The two chromatids are attached at a region called the centromere. The chromatids separate from each other when the nucleus divides just prior to cell division. Thus, each new cell that results after cell division will have the complete amount of genetic material, identical to the original, or parent, cell. In human cells, this amounts to 46 chromosomes. These chromosomes come in pairs (one from each pair inherited from each parent). So these 46 chromosomes are actually two sets of 23 chromosomes each.

 

 

Figure 2: A representation of a condensed eukaryotic chromosome, as seen after the DNA has been copied. The chromosome is made of two identical, or sister, chromatids held together by a centromere.

Each human somatic cell (a body cell, or every cell other than a gamete) normally has two sets of chromosomes, one set inherited from each parent. Each set contains 23 chromosomes, for a total of 46 chromosomes. Each chromosome differs in size, from over 250 million nucleotide pairs to less than 50 million nucleotide pairs. Each chromosome contains a specific set of genes, making each chromosome essential to survival.

Each pair of chromosomes consists of two chromosomes that are similar in size, shape, and genes. These pairs of chromosomes are known as homologous chromosomes, or homologues. Upon fertilization, a zygote is formed (Figure 3). A zygote is the first cell of a new individual. In humans, a zygote contains 23 pairs (or two sets) of chromosomes. Any cell containing two sets of chromosomes is said to be diploid. The zygote forms from the fusion of two haploid gametes. A haploid cell contains one set of chromosomes. In humans, a haploid gamete contains 23 chromosomes. Biologists use the symbol n to represent one set of chromosomes, and 2n to represent two sets. In humans, each set of chromosomes contains 22 autosomes and 1 sex chromosome. Autosomes are chromosomes that are not directly involved in determining the sex of an individual. The sex chromosomes contain genes that determine the sex of an individual.

 

 

Figure 3: Upon fertilization a diploid zygote is formed. In humans, a zygote has 46 chromosomes, 23 inherited from each parent. The gametes, sperm and eggs, are haploid cells, with 23 chromosomes each.

Whereas autosomes are found as homologous pairs in somatic cells, sex chromosomes come in two different sizes, shapes, and contain different genes. In many organisms, including humans, the sex chromosomes are known as the X and Y chromosomes. The Y chromosome contains genes that cause male development. Therefore, any individual with a Y chromosome is male, and a male will have both an X and Y chromosome (XY). Females, without a Y chromosome, will have two X chromosomes (XX). As females have two X chromosomes, they must pass an X chromosome to all of their children. As males have both an X chromosome (inherited from their mother) and a Y chromosome, they can give either chromosome to their children. If a child inherits a Y from his father, he will be male; if a child inherits an X from her father, she will be female. It therefore is the male gamete that determines the sex of the offspring.

The Cell Cycle

Cell division in eukaryotic cells is much more complex than in prokaryotic cells because of the many chromosomes within the nucleus. Both the cytoplasm and the genetic material must be divided, ensuring that each resulting daughter cell receives 46 separate chromosomes. To ensure this, in addition to the cell performing its necessary functions, the DNA must be copied, as must many organelles, prior to cell division.

The life of a eukaryotic cell is a cycle, known as the cell cycle (Figure 4). The cell cycle is a repeating series of cellular growth and division. The cell cycle has five phases: the first growth (\(G_{1}\)) phase, the synthesis (S) phase, the second growth (\(G_{2}\)) phase, mitosis, and cytokinesis, though many consider mitosis and cytokinesis to be combined into one phase. The cell spends the majority of the cycle in the first three phases of the cycle, collectively known as interphase. After cytokinesis, two genetically identical daughter cells are formed.

 

 

Figure 4: The Cell Cycle. The cell cycle depicts the life of an eukaryotic cell. The cell cycle has five phases: the first growth (\(G_{1}\)) phase, the synthesis (S) phase, the second growth (\(G_{2}\)) phase, mitosis (M), and cytokinesis (C). The cell spends the majority of the cycle in the first three phases (\(G_{1}\), S, \(G_{2}\)) of the cycle, collectively known as interphase. After cytokinesis, two genetically identical daughter cells are formed. Many consider the cell cycle to only have four phases, with mitosis and cytokinesis combined.

The first growth (\(G_{1}\)) phase: The cell spends most of its life in the \(G_{1}\) phase. During this phase, a cell undergoes rapid growth and the cell performs its routine functions. If a cell is not dividing, the cell remains in this phase.

The synthesis (S) phase: For two genetically identical daughter cells to be formed, the cell’s DNA must be copied or replicated. When the DNA is replicated, both strands of the double helix are used as templates to produce two new complementary strands. These new strands then hydrogen bond to the template strands and two double helices form.

The second growth (\(G_{2}\)) phase is a shortened growth period in which many organelles are reproduced or manufactured. Parts necessary for cell division are made during \(G_{2}\).

Mitosis is the phase of nuclear division, in which one nucleus divides and becomes two nuclei. After mitosis is cytokinesis, in which the cytoplasm divides in half, producing two daughter cells, each containing a complete set of genetic material.

Mitosis

Mitosis is the division of the cell’s nucleus, the final step before two daughter cells are produced. The cell enters mitosis as it approaches its size limitations. Four distinct phases of mitosis have been recognized: prophase, metaphase, anaphase, and telophase, with each phase merging into the next one (Figure 5).

 

 

Figure 5: During mitosis, the nucleus divides, paving the way for two cells to be produced after cell division, each with a complete makeup of genetic material.

Prophase is the first and longest phase of mitosis. During prophase, the DNA coils up into visible chromosomes, each made up of two sister chromatids held together by the centromere. The nucleus disappears as the nuclear envelope and nucleolus break apart. The centrioles begin to move to opposite ends, or poles, of the cell. As the centrioles migrate, the fiber-like spindle begins to elongate between the centrioles. The spindle is a thin, cage-like structure made out of microtubules. In plant cells, the spindle forms without centrioles. The spindle plays an essential role moving chromosomes and in the separation of sister chromatids.

During metaphase the spindle attaches to the centromere of each chromosome. Helped by the spindle, the chromosomes line up at the center, or equator, of the cell, also known as the metaphase plate. Each sister chromatid is attached to a separate spindle fiber, with one fiber extending to one pole, and the other fiber extending to the other pole. This ensures that the sister chromatids separate and end up in distinct cells after cell division.

Anaphase is the phase in which the sister chromatids separate. The sister chromatids are pulled apart by the shortening of the microtubules of the spindles, similar to the reeling in of a fish by the shortening of the fishing line. One sister chromatid moves to one pole of the cell, and the other sister chromatid moves to the opposite pole. At the end of anaphase, each pole of the cell has a complete set of chromosomes, identical to the amount of DNA at the beginning of \(G_{1}\) of the cell cycle.

Telophase is essentially the opposite of prophase. The chromosomes begin to unwind in preparation to direct the cell’s metabolic activities. The spindle begins to break down, allowing a new nucleus to form. This is followed by cytokinesis, the division of the cytoplasm, resulting in two genetically identical cells, ready to enter \(G_{1}\) of the next cell cycle. The phases of mitosis are summarized in Figure 6.

 

 

Figure 6: Mitosis. The phases of mitosis are depicted. The second phase, metaphase, is shown with the chromosomes lined up at the equator of the cell and the microtubule spindle fibers extending from the centrioles to the centromeres of the chromosomes.

Cytokinesis (Figure 7) differs between plant and animal cells. In animal cells, the plasma membrane pinches inward along the cell’s equator until two cells are formed. In plant cells, a cell plate forms along the cells equator. A new membrane grows along each side of the cell plate, with a new cell wall forming on the outside of each new membrane.

 

 

Figure 7: Cytokinesis. In this electron micrograph of a cell, two formation of two new cells is almost complete, as new membrane grows and divides the parent cell.

Control of the Cell Cycle

How does the cell know when to divide? How does the cell know when to replicate the DNA? The answers to these questions have to do with the control of the cell cycle. But how is the cell cycle controlled?

The cell cycle is controlled by a number of protein-controlled feedback processes. Two types of proteins involved in the control of the cell cycle are kinases and cyclins. Cyclins activate kinases. Cyclins are a group of proteins that is rapidly produced at key stages in the cell cycle. Kinases activate other target molecules. It is this precise regulation of proteins that triggers advancement through the cell cycle.

The cell cycle has key checkpoints. When the cell receives key signals or information (feedback regulation), the cell can begin the next phase of the cell cycle. The cell can also receive signals that delay passage to the next phase of the cell cycle. These signals allow the cell to complete the previous phase before moving forward. Three key checkpoints are the cell growth (\(G_{1}\)) checkpoint, the DNA synthesis (\(G_{2}\)) checkpoint, and the mitosis checkpoint.

The cell growth (\(G_{1}\)) checkpoint allows the cell to proceed into the S phase of the cell cycle and continue on to divide. The cell spends most of the cycle in the \(G_{1}\) phase. \(G_{1}\) is where the cell carries out its main functions. If the cell has performed its functions and has grown to significant size to be divided in half, key proteins will stimulate DNA replication to begin. If the cells are not to divide, such as some muscle and nerve cells, the cell will stop at this checkpoint and move into a resting phase. Some cells may stay in this resting period permanently, never dividing.

The DNA synthesis (\(G_{2}\)) checkpoint determines if the cell is ready for mitosis. DNA repair enzymes check the replicated DNA at this point. If the checkpoint is passed, the many molecular mechanisms and processes needed for mitosis will begin.

The mitosis checkpoint determines the end of one cycle and the beginning of the next. This checkpoint signals the end of mitosis, allowing the cell to prepare for the beginning of \(G_{1}\) of the next cell cycle.

Cancer and the Cell Cycle

Many cancers result from uncontrolled cell division, when the regulation of the cycle is lost (Figure 8). Cancerous cells divide much more rapidly than healthy cells. These cells use the blood and nutrients that other cells need and they can stress the environment of the healthy cells. As cancerous cells do not provide any useful function to the organism, they are extremely harmful. If cancerous cells are allowed to grow uncontrolled, they will kill the host organism. Many cancerous cells are the products of normal cells that have lost the ability to regulate the cell cycle. The genes that encode the proteins involved in cell cycle regulation have mutations. One category of genes, called oncogenes, accelerate the cell cycle. Many cancers can be inherited, such as breast cancer. Others are triggered by an environmental stimulus, such as through the relationship between tobacco smoke and lung cancer, or ultraviolet radiation and skin cancer.

 

 

Figure 8: When normal cells are damaged beyond repair, they are eliminated. (A) diagrams damaged cells being destroyed. Cancer cells avoid elimination and, because of uncontrolled cell division, continue to multiply in an unregulated manner. (B) depicts damaged cells dividing in an uncontrolled fashion.