10: Cell Reproduction

Question 1

What is the cell cycle?

Answer 1

The ordered sequence of events that a cell passes through between one cell division and the next.

Question 2

What is a centromere?

Answer 2

The region at which sister chromatids are bound together; a constricted area in condensed chromosomes.

Question 3

What is a chromatid?

Answer 3

A single DNA molecule of two strands of duplicated DNA and associated proteins held together at the centromere.

Question 4

What does it mean to be diploid?

Answer 4

A cell, nucleus, or organism containing two sets of chromosomes (2n).

Question 5

What is a gamete?

Answer 5

A haploid reproductive cell or sex cell (sperm, pollen grain, or egg).

Question 6

What is a gene?

Answer 6

The physical and functional unit of heredity, a sequence of DNA that codes for a protein.

Question 7

What is a genome?

Answer 7

The total genetic information of a cell or organism.

Question 8

What does it mean to be haploid?

Answer 8

A cell, nucleus, or organism containing one set of chromosomes.

Question 9

What is a histone?

Answer 9

A histone is one of several similar, highly conserved, low molecular weight, basic proteins found in the chromatin of all eukaryotic cells; associates with DNA to form nucleosomes.

Question 10

What are homologous chromosomes?

Answer 10

Chromosomes of the same morphology with genes in the same location; diploid organisms have pairs of homologous chromosomes (homologs), with each homolog derived from a different parent.

Question 11

What is a locus?

Answer 11

The position of a gene on a chromosome.

Question 12

What is a nucleosome?

Answer 12

A subunit of chromatin composed of a short length of DNA wrapped around a core of histone proteins.

Question 13

How is DNA organized in prokaryotes?

Answer 13

In prokaryotes, the genome is composed of a single, double-stranded DNA molecule in the form of a loop or circle. The region in the cell containing this genetic material is called a nucleoid.

Question 14

What are plasmids?

Answer 14

Some prokaryotes have smaller loops of DNA called plasmids that are not essential for normal growth. Bacteria can exchange these plasmids with other bacteria, sometimes receiving beneficial new genes that the recipient can add to their chromosomal DNA. Antibiotic resistance is one trait that often spreads through a bacterial colony through plasmid exchange.

Question 15

How is DNA organized in eukaryotes?

Answer 15

In eukaryotes, the genome consists of several double-stranded linear DNA molecules. Each species of eukaryotes has a characteristic number of chromosomes in the nuclei of its cells.

Question 16

How many chromosomes do humans have?

Answer 16

Human body cells have 46 chromosomes, while human gametes (sperm or eggs) have 23 chromosomes each.

Question 17

What is the difference between human somatic cells and gametes?

Answer 17

A typical body cell, or somatic cell, contains two matched sets of chromosomes, a configuration known as diploid. Human cells that contain one set of chromosomes are called gametes, or sex cells; these are eggs and sperm, and are designated 1n, or haploid.

Question 18

How can chromosomes be viewed?

Answer 18

The condensed chromosomes can be removed from a cell in mitosis and spread out on a slide, and artificially arranged according to length; an arrangement like this is called a karyotype. The chromosomes are exposed to fluorescent stains for differentiation of the different chromosomes. A method of staining called “chromosome painting” employs fluorescent dyes that highlight chromosomes in different colors.

Question 19

How are homologous chromosomes different from each other?

Answer 19

Each copy of a homologous pair of chromosomes originates from a different parent; therefore, the genes themselves are not identical. The variation of individuals within a species is due to the specific combination of the genes inherited from both parents. Even a slightly altered sequence of nucleotides within a gene can result in an alternative trait.

Question 20

How is blood type determined by homologous chromosomes?

Answer 20

For example, there are three possible gene sequences on the human chromosome that code for blood type: sequence A, sequence B, and sequence O. Because all diploid human cells have two copies of the chromosome that determines blood type, the blood type (the trait) is determined by which two versions of the marker gene are inherited. It is possible to have two copies of the same gene sequence on both homologous chromosomes, with one on each (for example, AA, BB, or OO), or two different sequences, such as AB.

Question 21

How much of a difference is there between homologous chromosomes?

Answer 21

Minor variations of traits, such as blood type, eye color, and handedness, contribute to the natural variation found within a species. However, if the entire DNA sequence from any pair of human homologous chromosomes is compared, the difference is less than one percent.

Question 22

What is the exception to homologous chromosome uniformity?

Answer 22

The sex chromosomes, X and Y, are the single exception to the rule of homologous chromosome uniformity: Other than a small amount of homology that is necessary to accurately produce gametes, the genes found on the X and Y chromosomes are different.

Question 23

How large is human DNA compared to the size of an average cell?

Answer 23

If the DNA from all 46 chromosomes in a human cell nucleus was laid out end to end, it would measure approximately two meters; however, its diameter would be only 2 nm, compared to the size of a typical human cell which is about 10 µm (100,000 cells lined up to equal one meter).

Question 24

How is eukaryotic DNA organized in a cell?

Answer 24

DNA must be tightly packaged to fit in the cell’s nucleus. At the same time, it must also be readily accessible for the genes to be expressed. During some stages of the cell cycle, the long strands of DNA are condensed into compact chromosomes. There are a number of ways that chromosomes are compacted.

Question 25

What is the first level of compaction of chromatin?

Answer 25

In the first level of compaction, short stretches of the DNA double helix wrap around a core of eight histone proteins at regular intervals along the entire length of the chromosome. The DNA-histone complex is called chromatin. The beadlike, histone DNA complex is called a nucleosome, and DNA connecting the nucleosomes is called linker DNA. A DNA molecule in this form is about seven times shorter than the double helix without the histones, and the beads are about 10 nm in diameter, in contrast with the 2-nm diameter of a DNA double helix.

Question 26

What is the second level of compaction of chromatin?

Answer 26

The next level of compaction occurs as the nucleosomes and the linker DNA between them are coiled into a 30-nm chromatin fiber. This coiling further shortens the chromosome so that it is now about 50 times shorter than the extended form.

Question 27

What is the third level of compaction of chromatin?

Answer 27

In the third level of packing, a variety of fibrous proteins is used to pack the chromatin. These fibrous proteins also ensure that each chromosome in a non-dividing cell occupies a particular area of the nucleus that does not overlap with that of any other chromosome.

Question 28

What are sister chromatids?

Answer 28

DNA replicates in the S phase of interphase. After replication, the chromosomes are composed of two linked sister chromatids. When fully compact, the pairs of identically packed chromosomes are bound to each other by cohesin proteins. The connection between the sister chromatids is closest in a region called the centromere. The conjoined sister chromatids, with a diameter of about 1 µm, are visible under a light microscope. The centromeric region is highly condensed and thus will appear as a constricted area.

Question 29

What is anaphase?

Answer 29

The stage of mitosis during which sister chromatids are separated from each other.

Question 30

What is a cell plate?

Answer 30

A structure formed during plant cell cytokinesis by Golgi vesicles, forming a temporary structure (phragmoplast) and fusing at the metaphase plate; ultimately leads to the formation of cell walls that separate the two daughter cells.

Question 31

What is a centriole?

Answer 31

A rod-like structure constructed of microtubules at the center of each animal cell centrosome.

Question 32

What is a cleavage furrow?

Answer 32

Constriction formed by an actin ring during cytokinesis in animal cells that leads to cytoplasmic division.

Question 33

What is condensin?

Answer 33

Proteins that help sister chromatids coil during prophase.

Question 34

What is cytokinesis?

Answer 34

Division of the cytoplasm following mitosis that forms two daughter cells.

Question 35

What is the G₀ phase?

Answer 35

A phase distinct from the G₁ phase of interphase; a cell in G₀ is not preparing to divide.

Question 36

What is the G₁ phase?

Answer 36

The first phase of interphase centered on cell growth during mitosis. AKA first gap.

Question 37

What is the G₂ phase?

Answer 37

The third phase of interphase during which the cell undergoes final preparations for mitosis. AKA second gap.

Question 38

What is interphase?

Answer 38

The period of the cell cycle leading up to mitosis; includes G₁, S, and G₂ phases (the interim period between two consecutive cell divisions).

Question 39

What is karyokinesis?

Answer 39

Mitotic nuclear division.

Question 40

What is a kinetochore?

Answer 40

A protein substructure associated with the centromere of each sister chromatid that attracts and binds spindle microtubules during prometaphase.

Question 41

What is the metaphase plate?

Answer 41

Equatorial plane midway between the two poles of a cell where the chromosomes align during metaphase.

Question 42

What is metaphase?

Answer 42

The stage of mitosis during which chromosomes are aligned at the metaphase plate.

Question 43

What is mitosis?

Answer 43

The period of the cell cycle during which the duplicated chromosomes are separated into identical nuclei; includes prophase, prometaphase, metaphase, anaphase, and telophase. AKA karyokinesis.

Question 44

What is the mitotic phase?

Answer 44

The period of the cell cycle during which duplicated chromosomes are distributed into two nuclei and cytoplasmic contents are divided; includes karyokinesis (mitosis) and cytokinesis.

Question 45

What is a mitotic spindle?

Answer 45

An apparatus composed of microtubules that orchestrates the movement of chromosomes during mitosis.

Question 46

What is prometaphase?

Answer 46

The stage of mitosis during which the nuclear membrane breaks down and mitotic spindle fibers attach to kinetochores.

Question 47

What is prophase?

Answer 47

The stage of mitosis during which chromosomes condense and the mitotic spindle begins to form.

Question 48

What is a quiescent cell?

Answer 48

A cell that is performing normal cell functions and has not initiated preparations for cell division.

Question 49

What is S phase?

Answer 49

The second, or synthesis, stage of interphase during which DNA replication occurs.

Question 50

What is telophase?

Answer 50

Stage of mitosis during which chromosomes arrive at opposite poles, decondense, and are surrounded by a new nuclear envelope.

Question 51

What are the main characteristics of the cell cycle?

Answer 51

The cell cycle is an ordered series of events involving cell growth and cell division that produces two new daughter cells. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages of growth, DNA replication, and division that produces two identical (clone) cells. The cell cycle has two major phases: interphase and the mitotic phase. During interphase, the cell grows and DNA is replicated. During the mitotic phase, the replicated DNA and cytoplasmic contents are separated, and the cell divides.

Question 52

What happens during interphase?

Answer 52

During interphase, the cell undergoes normal growth processes while also preparing for cell division. In order for a cell to move from interphase into the mitotic phase, many internal and external conditions must be met. The three stages of interphase are called G1, S, and G2.

Question 53

What happens during G₁ phase?

Answer 53

The first stage of interphase is called the G₁ phase (first gap) because, from a microscopic aspect, little change is visible. However, during the G₁ stage, the cell is quite active at the biochemical level. The cell is accumulating the building blocks of chromosomal DNA and the associated proteins as well as accumulating sufficient energy reserves to complete the task of replicating each chromosome in the nucleus.

Question 54

What happens during S phase?

Answer 54

Throughout interphase, nuclear DNA remains in a semi-condensed chromatin configuration. In the S phase, DNA replication can proceed through the mechanisms that result in the formation of identical pairs of DNA molecules—sister chromatids—that are firmly attached to the centromeric region. The centrosome is duplicated during the S phase. The two centrosomes will give rise to the mitotic spindle, the apparatus that orchestrates the movement of chromosomes during mitosis. At the center of each animal cell, the centrosomes of animal cells are associated with a pair of rod-like objects, the centrioles, which are at right angles to each other. Centrioles help organize cell division. Centrioles are not present in the centrosomes of other eukaryotic species, such as plants and most fungi.

Question 55

What happens during G₂ phase?

Answer 55

In the G₂ phase, the cell replenishes its energy stores and synthesizes proteins necessary for chromosome manipulation. Some cell organelles are duplicated, and the cytoskeleton is dismantled to provide resources for the mitotic phase. There may be additional cell growth during G₂. The final preparations for the mitotic phase must be completed before the cell is able to enter the first stage of mitosis.

Question 56

What happens during the mitotic phase?

Answer 56

The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and move into two new, identical daughter cells. The first portion of the mitotic phase is called karyokinesis, or nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into the two daughter cells.

Question 57

What happens during prophase?

Answer 57

During prophase, the “first phase,” the nuclear envelope starts to dissociate into small vesicles, and the membranous organelles (such as the Golgi apparatus and endoplasmic reticulum), fragment and disperse toward the periphery of the cell. The nucleolus disappears (disperses). The centrosomes begin to move to opposite poles of the cell. Microtubules that will form the mitotic spindle extend between the centrosomes, pushing them farther apart as the microtubule fibers lengthen. The sister chromatids begin to coil more tightly with the aid of condensin proteins and become visible under a light microscope.

Question 58

What happens during prometaphase?

Answer 58

During prometaphase, the “first change phase,” many processes that were begun in prophase continue to advance. The remnants of the nuclear envelope fragment. The mitotic spindle continues to develop as more microtubules assemble and stretch across the length of the former nuclear area. Chromosomes become more condensed and discrete. Each sister chromatid develops a protein structure called a kinetochore in the centromeric region. The proteins of the kinetochore attract and bind mitotic spindle microtubules. As the spindle microtubules extend from the centrosomes, some of these microtubules come into contact with and firmly bind to the kinetochores. Once a mitotic fiber attaches to a chromosome, the chromosome will be oriented until the kinetochores of sister chromatids face the opposite poles. Eventually, all the sister chromatids will be attached via their kinetochores to microtubules from opposing poles. Spindle microtubules that do not engage the chromosomes are called polar microtubules. These microtubules overlap each other midway between the two poles and contribute to cell elongation. Astral microtubules are located near the poles, aid in spindle orientation, and are required for the regulation of mitosis.

Question 59

What happens during metaphase?

Answer 59

During metaphase, the “change phase,” all the chromosomes are aligned in a plane called the metaphase plate, or the equatorial plane, midway between the two poles of the cell. The sister chromatids are still tightly attached to each other by cohesin proteins. At this time, the chromosomes are maximally condensed.

Question 60

What happens during anaphase?

Answer 60

During anaphase, the “upward phase,” the cohesin proteins degrade, and the sister chromatids separate at the centromere. Each chromatid, now called a chromosome, is pulled rapidly toward the centrosome to which its microtubule is attached. The cell becomes visibly elongated (oval shaped) as the polar microtubules slide against each other at the metaphase plate where they overlap.

Question 61

What happens during telophase?

Answer 61

During telophase, the “distance phase,” the chromosomes reach the opposite poles and begin to decondense (unravel), relaxing into a chromatin configuration. The mitotic spindles are depolymerized into tubulin monomers that will be used to assemble cytoskeletal components for each daughter cell. Nuclear envelopes form around the chromosomes, and nucleosomes appear within the nuclear area.

Question 62

What does cytokinesis do?

Answer 62

Cytokinesis, or “cell motion,” is the second main stage of the mitotic phase during which cell division is completed via the physical separation of the cytoplasmic components into two daughter cells. Division is not complete until the cell components have been apportioned and completely separated into the two daughter cells. Although the stages of mitosis are similar for most eukaryotes, the process of cytokinesis is quite different for eukaryotes that have cell walls, such as plant cells.

Question 63

What happens during cytokinesis in animal cells?

Answer 63

In cells such as animal cells that lack cell walls, cytokinesis follows the onset of anaphase. A contractile ring composed of actin filaments forms just inside the plasma membrane at the former metaphase plate. The actin filaments pull the equator of the cell inward, forming a fissure. This fissure, or “crack,” is called the cleavage furrow. The furrow deepens as the actin ring contracts, and eventually the membrane is cleaved in two.

Question 64

What happens during cytokinesis in plant cells?

Answer 64

In plant cells, a new cell wall must form between the daughter cells. During interphase, the Golgi apparatus accumulates enzymes, structural proteins, and glucose molecules prior to breaking into vesicles and dispersing throughout the dividing cell. During telophase, these Golgi vesicles are transported on microtubules to form a phragmoplast (a vesicular structure) at the metaphase plate. There, the vesicles fuse and coalesce from the center toward the cell walls; this structure is called a cell plate. As more vesicles fuse, the cell plate enlarges until it merges with the cell walls at the periphery of the cell. Enzymes use the glucose that has accumulated between the membrane layers to build a new cell wall. The Golgi membranes become parts of the plasma membrane on either side of the new cell wall.

Question 65

What happens during G₀ phase?

Answer 65

Cells in G₀ phase are not actively preparing to divide. The cell is in a quiescent (inactive) stage that occurs when cells exit the cell cycle. Some cells enter G₀ temporarily until an external signal triggers the onset of G₁. Other cells that never or rarely divide, such as mature cardiac muscle and nerve cells, remain in G₀ permanently.

Question 66

What is a cell cycle checkpoint?

Answer 66

The mechanism that monitors the preparedness of a eukaryotic cell to advance through the various cell cycle stages.

Question 67

What is cyclin?

Answer 67

One of a group of proteins that act in conjunction with cyclin-dependent kinases to help regulate the cell cycle by phosphorylating key proteins; the concentrations of cyclins fluctuate throughout the cell cycle.

Question 68

What is cyclin-dependent kinase?

Answer 68

One of a group of protein kinases that helps to regulate the cell cycle when bound to cyclin; it functions to phosphorylate other proteins that are either activated or inactivated by phosphorylation.

Question 69

What is p21?

Answer 69

A cell cycle regulatory protein that inhibits the cell cycle; its levels are controlled by p53.

Question 70

What is p53?

Answer 70

A cell cycle regulatory protein that regulates cell growth and monitors DNA damage; it halts the progression of the cell cycle in cases of DNA damage and may induce apoptosis.

Question 71

What is a retinoblastoma protein (Rb)?

Answer 71

A regulatory molecule that exhibits negative effects on the cell cycle by interacting with a transcription factor (E2F).

Question 72

How long is the cell cycle?

Answer 72

The length of the cell cycle is highly variable, even within the cells of a single organism. In humans, the frequency of cell turnover ranges from a few hours in early embryonic development, to an average of two to five days for epithelial cells, and to an entire human lifetime spent in G0 by specialized cells, such as cortical neurons or cardiac muscle cells.

Question 73

How long is each phase of the cell cycle?

Answer 73

There is also variation in the time that a cell spends in each phase of the cell cycle. When fast-dividing mammalian cells are grown in culture (outside the body under optimal growing conditions), the length of the cycle is about 24 hours. In rapidly dividing human cells with a 24-hour cell cycle, the G₁ phase lasts approximately nine hours, the S phase lasts 10 hours, the G₂ phase lasts about four and one-half hours, and the M phase lasts approximately one-half hour. In early embryos of fruit flies, the cell cycle is completed in about eight minutes. The timing of events in the cell cycle is controlled by mechanisms that are both internal and external to the cell.

Question 74

What are some conditions under which cell division may be activated or inhibited?

Answer 74

Both the initiation and inhibition of cell division are triggered by events external to the cell when it is about to begin the replication process. An event may be as simple as the death of a nearby cell or as sweeping as the release of growth-promoting hormones, such as human growth hormone (HGH). Crowding of cells can also inhibit cell division. Another factor that can initiate cell division is the size of the cell; as a cell grows, it becomes inefficient due to its decreasing surface-to-volume ratio. The solution to this problem is to divide.

Question 75

What happens when too much or too little HGH is active?

Answer 75

A lack of HGH can inhibit cell division, resulting in dwarfism, whereas too much HGH can result in gigantism.

Question 76

How can cell division be halted?

Answer 76

It is essential that the daughter cells produced be exact duplicates of the parent cell. Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be passed forward to every new cell produced from an abnormal cell. To prevent a compromised cell from continuing to divide, there are internal control mechanisms that operate at three main cell cycle checkpoints.

Question 77

Where do cell cycle checkpoints occur?

Answer 77

These checkpoints occur near the end of G₁, at the G₂/M transition, and during metaphase.

Question 78

What does the G₁ checkpoint do?

Answer 78

The G₁ checkpoint determines whether all conditions are favorable for cell division to proceed. The G₁ checkpoint, also called the restriction point (in yeast), is a point at which the cell irreversibly commits to the cell division process. External influences, such as growth factors, play a large role in carrying the cell past the G₁ checkpoint. In addition to adequate reserves and cell size, there is a check for genomic DNA damage at the G₁ checkpoint. A cell that does not meet all the requirements will not be allowed to progress into the S phase. The cell can halt the cycle and attempt to remedy the problematic condition, or the cell can advance into G₀ and await further signals when conditions improve.

Question 79

What does the G₂ checkpoint do?

Answer 79

The G₂ checkpoint bars entry into the mitotic phase if certain conditions are not met. As at the G₁ checkpoint, cell size and protein reserves are assessed. However, the most important role of the G₂ checkpoint is to ensure that all of the chromosomes have been replicated and that the replicated DNA is not damaged. If the checkpoint mechanisms detect problems with the DNA, the cell cycle is halted, and the cell attempts to either complete DNA replication or repair the damaged DNA.

Question 80

What does the M checkpoint do?

Answer 80

The M checkpoint occurs near the end of the metaphase stage of karyokinesis. The M checkpoint is also known as the spindle checkpoint, because it determines whether all the sister chromatids are correctly attached to the spindle microtubules. Because the separation of the sister chromatids during anaphase is an irreversible step, the cycle will not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to at least two spindle fibers arising from opposite poles of the cell.

Question 81

How are regulator molecules used in cell division?

Answer 81

In addition to the internally controlled checkpoints, there are two groups of intracellular molecules that regulate the cell cycle. These regulatory molecules either promote progress of the cell to the next phase (positive regulation) or halt the cycle (negative regulation). Regulator molecules may act individually, or they can influence the activity or production of other regulatory proteins. Therefore, the failure of a single regulator may have almost no effect on the cell cycle, especially if more than one mechanism controls the same event. Conversely, the effect of a deficient or non-functioning regulator can be wide-ranging and possibly fatal to the cell if multiple processes are affected.

Question 82

Which molecules positively regulate cell division?

Answer 82

Two groups of proteins, called cyclins and cyclin-dependent kinases (Cdks), are responsible for the progress of the cell through the various checkpoints. The levels of the four cyclin proteins fluctuate throughout the cell cycle in a predictable pattern. Increases in the concentration of cyclin proteins are triggered by both external and internal signals. After the cell moves to the next stage of the cell cycle, the cyclins that were active in the previous stage are degraded.

Question 83

How do Cdk/cyclin complexes regulate cell division?

Answer 83

Cyclins regulate the cell cycle only when they are tightly bound to Cdks. To be fully active, the Cdk/cyclin complex must also be phosphorylated in specific locations. Like all kinases, Cdks are enzymes (kinases) that phosphorylate other proteins. Phosphorylation activates the protein by changing its shape. The proteins phosphorylated by Cdks are involved in advancing the cell to the next phase. The levels of Cdk proteins are relatively stable throughout the cell cycle; however, the concentrations of cyclin fluctuate and determine when Cdk/cyclin complexes form. The different cyclins and Cdks bind at specific points in the cell cycle and thus regulate different checkpoints.

Since the cyclic fluctuations of cyclin levels are based on the timing of the cell cycle and not on specific events, regulation of the cell cycle usually occurs by either the Cdk molecules alone or the Cdk/cyclin complexes. Without a specific concentration of fully activated cyclin/Cdk complexes, the cell cycle cannot proceed through the checkpoints.

Question 84

How are Cdks negatively regulated?

Answer 84

Although the cyclins are the main regulatory molecules that determine the forward momentum of the cell cycle, there are several other mechanisms that fine-tune the progress of the cycle with negative, rather than positive, effects. These mechanisms essentially block the progression of the cell cycle until problematic conditions are resolved. Molecules that prevent the full activation of Cdks are called Cdk inhibitors. Many of these inhibitor molecules directly or indirectly monitor a particular cell cycle event. The block placed on Cdks by inhibitor molecules will not be removed until the specific event that the inhibitor monitors is completed.

Question 85

What are some negative regulatory molecules?

Answer 85

The best understood negative regulatory molecules are retinoblastoma protein (Rb), p53, and p21. Retinoblastoma proteins are a group of tumor-suppressor proteins common in many cells. The 53 and 21 designations refer to the functional molecular masses of the proteins (p) in kilodaltons. Much of what is known about cell cycle regulation comes from research conducted with cells that have lost regulatory control. All three of these regulatory proteins were discovered to be damaged or non-functional in cells that had begun to replicate uncontrollably (became cancerous). In each case, the main cause of the unchecked progress through the cell cycle was a faulty copy of the regulatory protein.

Question 86

Where do negative regulatory molecules operate?

Answer 86

Rb, p53, and p21 act primarily at the G₁ checkpoint.

Question 87

How do p53 and p21 work?

Answer 87

p53 is a multi-functional protein that has a major impact on the commitment of a cell to division because it acts when there is damaged DNA in cells that are undergoing the preparatory processes during G₁. If damaged DNA is detected, p53 halts the cell cycle and recruits enzymes to repair the DNA. If the DNA cannot be repaired, p53 can trigger apoptosis, or cell suicide, to prevent the duplication of damaged chromosomes. As p53 levels rise, the production of p21 is triggered. p21 enforces the halt in the cycle dictated by p53 by binding to and inhibiting the activity of the Cdk/cyclin complexes. As a cell is exposed to more stress, higher levels of p53 and p21 accumulate, making it less likely that the cell will move into the S phase.

Question 88

How does Rb work?

Answer 88

Rb exerts its regulatory influence on other positive regulator proteins. Chiefly, Rb monitors cell size. In the active, dephosphorylated state, Rb binds to proteins called transcription factors, most commonly, E2F. When Rb is bound to E2F, production of proteins necessary for the G₁/S transition is blocked. As the cell increases in size, Rb is slowly phosphorylated until it becomes inactivated. Rb releases E2F, which can now turn on the gene that produces the transition protein, and this particular block is removed. For the cell to move past each of the checkpoints, all positive regulators must be “turned on,” and all negative regulators must be “turned off.”

Question 89

What is an oncogene?

Answer 89

A mutated version of a normal gene involved in the positive regulation of the cell cycle.

Question 90

What is a proto-oncogene?

Answer 90

A normal gene that when mutated becomes an oncogene.

Question 91

What is a tumor suppressor gene?

Answer 91

A segment of DNA that codes for negative cell cycle regulatory proteins that prevent the cell from undergoing uncontrolled division.

Question 92

How does cancer occur?

Answer 92

Cancer comprises many different diseases caused by a common mechanism: uncontrolled cell growth. Despite the redundancy and overlapping levels of cell cycle control, errors do occur. One of the critical processes monitored by the cell cycle checkpoint surveillance mechanism is the proper replication of DNA during the S phase. Even when all of the cell cycle controls are fully functional, a small percentage of replication errors (mutations) will be passed on to the daughter cells. If changes to the DNA nucleotide sequence occur within a coding portion of a gene and are not corrected, a gene mutation results. All cancers start when a gene mutation gives rise to a faulty protein that plays a key role in cell reproduction. The change in the cell that results from the malformed protein may be minor: perhaps a slight delay in the binding of Cdk to cyclin or an Rb protein that detaches from its target DNA while still phosphorylated. Even minor mistakes, however, may allow subsequent mistakes to occur more readily. Over and over, small uncorrected errors are passed from the parent cell to the daughter cells and amplified as each generation produces more non-functional proteins from uncorrected DNA damage. Eventually, the pace of the cell cycle speeds up as the effectiveness of the control and repair mechanisms decreases. Uncontrolled growth of the mutated cells outpaces the growth of normal cells in the area, and a tumor (“-oma”) can result.

Question 93

How can proto-oncogenes cause cancer?

Answer 93

The genes that code for the positive cell cycle regulators are called proto-oncogenes. Proto-oncogenes are normal genes that, when mutated in certain ways, become oncogenes, genes that cause a cell to become cancerous. Consider what might happen to the cell cycle in a cell with a recently acquired oncogene. In most instances, the alteration of the DNA sequence will result in a less functional (or non-functional) protein. The result is detrimental to the cell and will likely prevent the cell from completing the cell cycle; however, the organism is not harmed because the mutation will not be carried forward. If a cell cannot reproduce, the mutation is not propagated and the damage is minimal. Occasionally, however, a gene mutation causes a change that increases the activity of a positive regulator. For example, a mutation that allows Cdk to be activated without being partnered with cyclin could push the cell cycle past a checkpoint before all of the required conditions are met. If the resulting daughter cells are too damaged to undergo further cell divisions, the mutation would not be propagated and no harm would come to the organism. However, if the atypical daughter cells are able to undergo further cell divisions, subsequent generations of cells will probably accumulate even more mutations, some possibly in additional genes that regulate the cell cycle.

Question 94

How do tumor suppressor genes prevent cancer?

Answer 94

Like proto-oncogenes, many of the negative cell cycle regulatory proteins were discovered in cells that had become cancerous. Tumor suppressor genes are segments of DNA that code for negative regulator proteins, the type of regulators that, when activated, can prevent the cell from undergoing uncontrolled division. The collective function of the best-understood tumor suppressor gene proteins, Rb, p53, and p21, is to put up a roadblock to cell cycle progression until certain events are completed. A cell that carries a mutated form of a negative regulator might not be able to halt the cell cycle if there is a problem. Tumor suppressors are similar to brakes in a vehicle: Malfunctioning brakes can contribute to a car crash.

Question 95

How can a faulty p53 gene cause cancer?

Answer 95

Mutated p53 genes have been identified in more than one-half of all human tumor cells. This discovery is not surprising in light of the multiple roles that the p53 protein plays at the G₁ checkpoint. A cell with a faulty p53 may fail to detect errors present in the genomic DNA. Even if a partially functional p53 does identify the mutations, it may no longer be able to signal the necessary DNA repair enzymes. Either way, damaged DNA will remain uncorrected. At this point, a functional p53 will deem the cell unsalvageable and trigger programmed cell death (apoptosis). The damaged version of p53 found in cancer cells, however, cannot trigger apoptosis.

Question 96

What are some other side effects of a faulty p53 gene?

Answer 96

The loss of p53 function has other repercussions for the cell cycle. Mutated p53 might lose its ability to trigger p21 production. Without adequate levels of p21, there is no effective block on Cdk activation. Essentially, without a fully functional p53, the G₁ checkpoint is severely compromised and the cell proceeds directly from G₁ to S regardless of internal and external conditions. At the completion of this shortened cell cycle, two daughter cells are produced that have inherited the mutated p53 gene. Given the non-optimal conditions under which the parent cell reproduced, it is likely that the daughter cells will have acquired other mutations in addition to the faulty tumor suppressor gene. Cells such as these daughter cells quickly accumulate both oncogenes and non-functional tumor suppressor genes. Again, the result is tumor growth.

Question 97

What is binary fission?

Answer 97

A prokaryotic cell division process.

Question 98

What is FtsZ?

Answer 98

A tubulin-like protein component of the prokaryotic cytoskeleton that is important in prokaryotic cytokinesis (name origin: (Filamenting temperature-sensitive mutant Z).

Question 99

What is an origin?

Answer 99

A region of the prokaryotic chromosome where replication begins (origin of replication). AKA ORI.

Question 100

What is a septum?

Answer 100

A structure formed in a bacterial cell as a precursor to the separation of the cell into two daughter cells.

Question 101

In what ways is cell division simpler in prokaryotes than in eukaryotes?

Answer 101

In bacterial cells, the genome consists of a single, circular DNA chromosome; therefore, the process of cell division is simplified. Karyokinesis is unnecessary because there is no nucleus and thus no need to direct one copy of the multiple chromosomes into each daughter cell.

Due to the relative simplicity of the prokaryotes, the cell division process, called binary fission, is a less complicated and much more rapid process than cell division in eukaryotes. The single, circular DNA chromosome of bacteria is not enclosed in a nucleus, but instead occupies a specific location, the nucleoid, within the cell. Although the DNA of the nucleoid is associated with proteins that aid in packaging the molecule into a compact size, there are no histone proteins and thus no nucleosomes in prokaryotes. The packing proteins of bacteria are, however, related to the cohesin and condensin proteins involved in the chromosome compaction of eukaryotes.

Question 102

What happens during binary fission?

Answer 102

The bacterial chromosome is attached to the plasma membrane at about the midpoint of the cell. The starting point of replication, the origin, is close to the binding site of the chromosome to the plasma membrane. Replication of the DNA is bidirectional, moving away from the origin on both strands of the loop simultaneously. As the new double strands are formed, each origin point moves away from the cell wall attachment toward the opposite ends of the cell. As the cell elongates, the growing membrane aids in the transport of the chromosomes. After the chromosomes have cleared the midpoint of the elongated cell, cytoplasmic separation begins. The formation of a ring composed of repeating units of a protein called FtsZ directs the partition between the nucleoids. Formation of the FtsZ ring triggers the accumulation of other proteins that work together to recruit new membrane and cell wall materials to the site. A septum is formed between the nucleoids, extending gradually from the periphery toward the center of the cell. When the new cell walls are in place, the daughter cells separate.

Question 103

In what ways is FtsZ in prokaryotes similar to the tubulin of mitotic spindles in eukaryotes?

Answer 103

The precise timing and formation of the mitotic spindle is critical to the success of eukaryotic cell division. Prokaryotic cells, on the other hand, do not undergo karyokinesis and therefore have no need for a mitotic spindle. However, the FtsZ protein that plays such a vital role in prokaryotic cytokinesis is structurally and functionally very similar to tubulin, the building block of the microtubules that make up the mitotic spindle fibers that are necessary for eukaryotes. FtsZ proteins can form filaments, rings, and other three-dimensional structures that resemble the way tubulin forms microtubules, centrioles, and various cytoskeletal components. In addition, both FtsZ and tubulin employ the same energy source, GTP (guanosine triphosphate), to rapidly assemble and disassemble complex structures.

Question 104

How has FtsZ and tubulin evolved over time?

Answer 104

FtsZ and tubulin are homologous structures derived from common evolutionary origins. FtsZ is the ancestor protein to tubulin (a modern protein). While both proteins are found in extant organisms, tubulin function has evolved and diversified tremendously since evolving from its FtsZ prokaryotic origin. A survey of mitotic assembly components found in present-day unicellular eukaryotes reveals crucial intermediary steps to the complex membrane-enclosed genomes of multicellular eukaryotes.