Concept 12.3: The eukaryotic cell cycle is regulated by a molecular control system

Question 1

The timing and rate of cell division in different parts of a plant or animal are crucial to

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normal growth, development, and maintenance.

Question 2

The frequency of cell division varies with the type of cell. For example, human skin cells divide frequently throughout life, whereas liver cells maintain the ability to divide but keep it in reserve until an appropriate need arises—say, to

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repair a wound.

Question 3

Some of the most specialized cells, such as fully formed nerve cells and muscle cells, do not

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divide at all in a mature human

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These cell cycle differences result from regulation at the

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molecular level.

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In the early 1970s, a variety of experiments led to the hypothesis that the

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cell cycle is driven by specific signaling molecules present in the cytoplasm.

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Some of the first strong evidence for this hypothesis came from experiments with mammalian cells grown in culture. In these experiments, two cells in different phases of the cell cycle were

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fused to form a single cell with two nuclei

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If one of the original cells was in the S phase and the other was in G1, the G1 nucleus immediately entered the S phase, as though stimulated by

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signaling molecules present in the cytoplasm of the first cell.

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Similarly, if a cell undergoing mitosis (M phase) was fused with another cell in any stage of its cell cycle, even G1, the second nucleus immediately entered mitosis, with condensation of the

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chromatin and formation of a mitotic spindle.

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Figure 12.14 inquiry

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a cyclically operating set of molecules in the cell that both triggers and coordinates key events in the cell cycle

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cell cycle control system

Question 11

Like the washer’s timing device, the cell cycle control system proceeds on its own, according to a .

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built-in clock

Question 12

However, just as a washer’s cycle is subject to both internal control (such as the sensor that detects when the tub is filled with water) and external adjustment (such as starting or stopping the machine), the cell cycle is regulated at certain checkpoints by both

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internal and external signals.

Question 13

_______________ in the cell cycle is a control point where stop and go-ahead signals can regulate the cycle

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checkpoint

Question 14

figure 12.15 mechanical analogy, animation control of the cell cycle

Question 15

Rhythmic fluctuations in the abundance and activity of cell cycle control molecules pace the

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sequential events of the cell cycle.

Question 16

These regulatory molecules are mainly proteins of two types:

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protein kinases and cyclins.

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are enzymes that activate or inactivate other proteins by phosphorylating them

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Protein kinases

Question 18

Many of the kinases that drive the cell cycle are actually present at a constant concentration in the growing cell, but much of the time they are in an

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inactive form.

Question 19

To be active, such a kinase must be attached to a _________, a protein that gets its name from its cyclically fluctuating concentration in the cell.

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cyclin,

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Because of this requirement, these kinases are called

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cyclin-dependent kinases, or Cdks.

Question 21

The activity of a Cdk rises and falls with changes in the concentration of its

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cyclin partner.

Question 22

a protein complex required for a cell to progress from late interphase to mitosis. the active form consists of cyclin and a protein kinase

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MPF

Question 23

figure 12.16 molecular control of the cell cycle at the G2 checkpoint

Question 24

The initials MPF stand for ________________________ but we can think of MPF as “M-phase-promoting factor” because it triggers the cell’s passage into the M phase, past the G2 checkpoint.

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“maturation-promoting factor,”

Question 25

When cyclins that accumulate during G2 associate with Cdk molecules, the resulting MPF complex is active—it phosphorylates a variety of proteins, initiating

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mitosis

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MPF acts both directly as a kinase and indirectly by activating

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other kinases.

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During anaphase, MPF helps switch itself off by initiating a process that leads to the

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destruction of its own cyclin

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The noncyclin part of MPF, the Cdk, persists in the cell, inactive until it becomes part of MPF again by associating with new cyclin molecules synthesized during the S and

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G2 phases of the next round of the cycle.

Question 29

The fluctuating activities of different cyclin-Cdk complexes are of major importance in controlling all the stages of the cell cycle; they also give the

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go-ahead signals at some checkpoints.

Question 30

Cell behavior at the G1 checkpoint is also regulated by the activity of

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cyclin-Cdk protein complexes

Question 31

Animal cells generally have built-in stop signals that halt the cell cycle at

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checkpoints until overridden by go-ahead signals

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Many signals registered at checkpoints come from cellular surveillance mechanisms inside the cell. These signals report whether crucial cellular processes that should have occurred by that point have in fact been completed correctly and thus whether or not the

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cell cycle should proceed.

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Checkpoints also register signals from outside the

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cell.

Question 34

Three important checkpoints are those in the

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G1,G2 , and M phases

Question 35

For many cells, the G1 checkpoint seems to be the most important. If a cell receives a go-ahead signal at the G1, S, G2, and M phases and divide. If it does not receive a go-ahead signal at that point, it may exit the cycle, switching into a nondividing state called the

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Gּּₒ phase

Question 36

Most cells of the human body are actually in the

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Gּּₒ phase.

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other cells, such as liver cells, can be ____________ from the Gּּₒ phase to the cell cycle by external cues, such as growth factors released during injury.

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“called back”

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figure 12.17

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Biologists are currently working out the pathways that link signals originating inside and outside the cell with the responses by

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cyclin-dependent kinases and other proteins.

Question 40

Anaphase, the separation of sister chromatids, does not begin until all the chromosomes are properly attached to the spindle at the

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metaphase plate

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Only when the kinetochores of all the chromosomes are properly attached to the spindle does the appropriate regulatory protein complex become

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activated.

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Once activated, the complex sets off a chain of molecular events that activates the enzyme separase, which cleaves the cohesins, allowing the

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sister chromatids to separate.

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checkpoint in S phase stops cells with DNA damage from

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proceeding in the cell cycle.

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in 2014, researchers presented evidence for another checkpoint between anaphase and telophase that ensures anaphase is completed and the chromosomes are well separated before cytokinesis can begin, thus avoiding

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chromosomal damage.

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cells fail to divide if an essential nutrient is lacking in the

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culture medium.

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is a protein released by certain cells that stimulates other cells to divide.

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growth factor

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Different cell types respond specifically to different

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growth factors or combinations of growth factors.

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platelet-derived growth factor (PDGF), which is made by blood cell fragments called

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platelets.

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PDGF is required for the division of cultured fibroblasts, a type of

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connective tissue cell.

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Fibroblasts have PDGF receptors on their

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plasma membranes.

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The binding of PDGF molecules to these receptors (which are receptor tyrosine kinases; see Figure 11.8) triggers a signal transduction pathway that allows the cells to pass the

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G1 checkpoint and divide.

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PDGF stimulates fibroblast division not only in the artificial conditions of cell culture but also in an animal’s body. When an injury occurs, platelets release PDGF in the vicinity. The resulting proliferation of fibroblasts helps

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heal the wound.

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Figure 12.18

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a phenomenon in which crowded cells stop dividing

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density-dependent inhibition,

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As first observed many years ago, cultured cells normally divide until they form a single layer of cells on the inner surface of a culture flask, at which point the cells stop dividing. If some cells are removed, those bordering the open space begin dividing again and continue until the

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vacancy is filled

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Follow-up studies revealed that the binding of a cell-surface protein to its counterpart on an adjoining cell sends a signal to both cells that inhibits cell division, preventing them from moving forward in the cell cycle, even in the presence of

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growth factors.

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To divide, they must be attached to a substratum, such as the inside of a culture flask or the extracellular matrix of a tissue.

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anchorage dependence

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figure 12.19

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Density-dependent inhibition and anchorage dependence appear to function not only in cell culture but also in the body’s tissues, checking the growth of cells at some optimal density and location during

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embryonic development and throughout an organism’s life.

Question 60

Cancer cells do not heed the normal signals that regulate the

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cell cycle.

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A logical hypothesis is that cancer cells do not need

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growth factors

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There are other important differences between normal cells and cancer cells that reflect derangements of the cell cycle. If and when they stop dividing, cancer cells do so at random points in the cycle, rather than at the

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normal checkpoints.

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Moreover, cancer cells can go on dividing indefinitely in culture if they are given a continual supply of nutrients; in essence, they are

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“immortal.”

Question 64

Cells of this line are called _____________ because their original source was a tumor removed from a woman named Henrietta Lacks.

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HeLa cells

Question 65

Cells in culture that acquire the ability to divide indefinitely are said to have undergone ________________, the process that causes them to behave like cancer cells.

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transformation

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By contrast, nearly all normal, nontransformed mammalian cells growing in culture divide only about 20 to 50 times before they stop

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dividing, age, and die.

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Finally, cancer cells evade the normal controls that trigger a cell to undergo apoptosis when something is wrong—for example, when an irreparable mistake has occurred during DNA replication preceding

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mitosis.

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The problem begins when a single cell in a tissue undergoes the first of many steps that converts a normal cell to a cancer cell. Such a cell often has altered proteins on its surface, and the body’s immune system normally recognizes the cell as

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“nonself”—an insurgent—and destroys it

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However, if the cell evades destruction, it may proliferate and form a

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tumor, a mass of abnormal cells within otherwise normal tissue.

Question 70

The abnormal cells may remain at the original site if they have too few genetic and cellular changes to survive at another site. In that case, the tumor is called a

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benign tumor

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includes cells whose genetic and cellular changes enable them to spread to new tissues and impair the functions of one or more organs

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malignant tumor

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these cells are also sometimes called

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transformed cells

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figure 12.20, video tumor growth in a living mouse

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The changes that have occurred in cells of malignant tumors show up in many ways besides excessive proliferation. These cells may have unusual numbers of

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chromosomes

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Abnormal changes on the cell surface cause cancer cells to lose attachments to neighboring cells and the extracellular matrix, allowing them to spread into

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nearby tissues.

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This spread of cancer cells to locations distant from their original site is called

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metastasis

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A tumor that appears to be localized may be treated with

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high-energy radiation,

Question 78

To treat known or suspected metastatic tumors,________________ is used, in which drugs that are toxic to actively dividing cells are administered through the circulatory system.

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chemotherapy

Question 79

video are fruit flies the key

Question 80

the cells of roughly 20% of breast cancer tumors show abnormally high amounts of a cell-surface receptor tyrosine kinase called ________, and many show an increase in the number of estrogen receptor (ER) molecules, intracellular receptors that can trigger cell division.

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HER2