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Learning Objectives Connection for AP® Courses Interphase The Mitotic Phase G0 Phase Disclaimer

Learning Objectives

In this section, you will explore the following questions:

What processes occur during the three stages of interphase?
How do the chromosomes behave during the mitotic phase?

Connection for AP® Courses

Connection for AP^® Courses

The cell cycle describes an orderly sequence of events that are highly regulated. In eukaryotes, the cell cycle consists of a long preparatory period (interphase) followed by mitosis and cytokinesis. Interphase is divided into three phases: Gap 1 (G₁), DNA synthesis (S), and Gap 2 (G₂). Interphase represents the portion of the cell cycle between nuclear divisions. During this phase, preparations are made for division that include growth, duplication of most cellular contents, and replication of DNA. The cell’s DNA is replicated during the S stage. (We will study the details of DNA replication in the chapter on DNA structure and function.) Following the G₂ stage of interphase, the cell begins mitosis, the process of active division by which duplicated chromosomes (chromatids) attach to spindle fibers, align themselves along the equator of the cell, and then separate from each other.

Following mitosis, the cell undergoes cytokinesis, the splitting of the parent cell into two daughter cells, complete with a full complement of genetic material. In animal cells, daughter cells are separated by an actin ring, whereas plant cells are separated by the cell plate, which will grow into a new cell wall. Sometimes cells enter a Gap zero (G₀) phase, during which they do not actively prepare to divide; the G₀ phase can be temporary until triggered by an external signal to enter G₁, or permanent, such as mature cardiac muscle cells and nerve cells.

Information presented and the examples highlighted in the section support concepts and Learning Objectives outlined in Big Idea 3 of the AP^® Biology Curriculum Framework, as shown in the tables. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP^® Biology course, an inquiry-based laboratory experience, instructional activities, and AP^® exam questions. A Learning Objective merges required content with one or more of the seven Science Practices.

Big Idea 3	Living systems store, retrieve, transmit, and respond to information essential to life processes.
Enduring Understanding 3.A	Heritable information provides for continuity of life.
Essential Knowledge	3.A.2 In eukaryotes, heritable information is passed to the next generation via processes that include the cell cycle and mitosis or meiosis plus fertilization.
Science Practice	6.4 The student can make claims and predictions about natural phenomena based on scientific theories and models.
Learning Objective	3.7 The student can make predictions about natural phenomena occurring during the cell cycle.
Essential Knowledge	3.A.2 In eukaryotes, heritable information is passed to the next generation via processes that include the cell cycle and mitosis or meiosis plus fertilization.
Science Practice	1.2 The student can describe representations and models of natural or man-made phenomena and systems in the domain.
Learning Objective	3.8 The student can describe the events that occur in the cell cycle.
Essential Knowledge	3.A.2 In eukaryotes, heritable information is passed to the next generation via processes that include the cell cycle and mitosis or meiosis plus fertilization.
Science Practice	5.3 The student can evaluate the evidence provided by data sets in relation to a particular scientific question.
Learning Objective	3.11 The student is able to evaluate evidence provided by data sets to support the claim that heritable information is passed from one generation to another generation through mitosis.

The Science Practices Assessment Ancillary contains additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards:

[APLO 2.35]
[APLO 2.15]
[APLO 2.19]
[APLO 3.11]
[APLO 2.33]
[APLO 2.36]
[APLO 2.37]
[APLO 2.31]

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 (Figure 10.6). 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.

Figure 10.6 The cell cycle consists of interphase and the mitotic phase. During interphase, the cell grows and the nuclear DNA is duplicated. Interphase is followed by the mitotic phase. During the mitotic phase, the duplicated chromosomes are segregated and distributed into daughter nuclei. The cytoplasm is usually divided as well, resulting in two daughter cells.

Interphase

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.

G₁ Phase (First Gap)

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.

S Phase (Synthesis of DNA)

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.

G₂ Phase (Second Gap)

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.

The Mitotic Phase

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.

Link to Learning

Revisit the stages of mitosis at this site.

Gout is a form of arthritis that causes a painful inflammation of joints. One treatment for gout is colchicine, a medication that inhibits mitosis. Explain why this medication is beneficial for people with gout and why it can cause undesirable side effects, such as low white blood cell counts.

Colchicine increases inflammation by inhibiting mitosis. Inhibition of mitosis results in decreased white blood count.
Colchicine decreases inflammation by inhibiting mitosis. Inhibition of mitosis results in decreased white blood count.
Colchicine increases inflammation by inhibiting mitosis. Inhibition of mitosis results in increased white blood count.
Colchicine decreases inflammation by inhibiting mitosis. Inhibition of mitosis results in increased white blood count.

Karyokinesis (Mitosis)

Karyokinesis, also known as mitosis, is divided into a series of phases—prophase, prometaphase, metaphase, anaphase, and telophase—that result in the division of the cell nucleus (Figure 10.8).

Everyday Connection for AP® Courses

These budding plants demonstrate asexual reproduction, one of the main purposes of mitosis. The other two purposes are growth and repair.

Photo shows small, green fleshy succulent sedum plants, growing as a ground cover. The plant has spread in a continuous mat, with new plants growing from offshoots of older plants.

Figure 10.7

Which of the following statements best describes the relationship between mitosis and asexual reproduction?

Mitosis is a process that can result in asexual reproduction.
Mitosis is a process that always results in asexual reproduction.
Asexual reproduction is a process that always results in mitosis.
Asexual reproduction is a process that can result in mitosis.

Visual Connection

This diagram shows the five phases of mitosis and cytokinesis. During prophase, the chromosomes condense and become visible, spindle fibers emerge from the centrosomes, the nuclear envelope breaks down, and the nucleolus disappears. During prometaphase, the chromosomes continue to condense and kinetochores appear at the centromeres. Mitotic spindle microtubules attach to the kinetochores, and centrosomes move toward opposite poles. During metaphase, the mitotic spindle is fully developed, and centrosomes

Figure 10.8 Karyokinesis (or mitosis) is divided into five stages—prophase, prometaphase, metaphase, anaphase, and telophase. The pictures at the bottom were taken by fluorescence microscopy (hence, the black background) of cells artificially stained by fluorescent dyes: blue fluorescence indicates DNA (chromosomes) and green fluorescence indicates microtubules (spindle apparatus). (credit mitosis drawings: modification of work by Mariana Ruiz Villareal; credit micrographs: modification of work by Roy van Heesbeen; credit cytokinesis micrograph: Wadsworth Center/New York State Department of Health; scale-bar data from Matt Russell)

Which of the following is the correct order of events in mitosis?

Sister chromatids line up at the metaphase plate. The kinetochore becomes attached to the mitotic spindle. The nucleus reforms and the cell divides. Cohesin proteins break down and the sister chromatids separate.
The kinetochore becomes attached to the mitotic spindle. Cohesin proteins break down and the sister chromatids separate. Sister chromatids line up at the metaphase plate. The nucleus reforms and the cell divides.
The kinetochore becomes attached to the cohesin proteins. Sister chromatids line up at the metaphase plate. The kinetochore breaks down and the sister chromatids separate. The nucleus reforms and the cell divides.
The kinetochore becomes attached to the mitotic spindle. Sister chromatids line up at the metaphase plate. Cohesin proteins break down and the sister chromatids separate. The nucleus reforms and the cell divides.

During prophase, the first phase, the nuclear envelope starts to dissociate into small vesicles, and the membranous organelles (such as the Golgi complex or 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.

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 (Figure 10.9). 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.

This illustration shows two sister chromatids. Each has a kinetochore at the centromere, and mitotic spindle microtubules radiate from the kinetochore.

Figure 10.9 During prometaphase, mitotic spindle microtubules from opposite poles attach to each sister chromatid at the kinetochore. In anaphase, the connection between the sister chromatids breaks down, and the microtubules pull the chromosomes toward opposite poles.

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.

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.

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.

Cytokinesis

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.

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 (Figure 10.10).

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 (Figure 10.10).

Part a: This illustration shows cytokinesis in a typical animal cell. Part b: Cytokinesis is shown in a typical plant cell. In an animal cell, a contractile ring of actin filaments forms a cleavage furrow that divides the cell in two. In a plant cell, Golgi vesicles coalesce at the metaphase plate. A cell plate grows from the center outward, and the vesicles form a plasma membrane that divides the cytoplasm.

Figure 10.10 During cytokinesis in animal cells, a ring of actin filaments forms at the metaphase plate. The ring contracts, forming a cleavage furrow, which divides the cell in two. In plant cells, Golgi vesicles coalesce at the former metaphase plate, forming a phragmoplast. A cell plate formed by the fusion of the vesicles of the phragmoplast grows from the center toward the cell walls, and the membranes of the vesicles fuse to form a plasma membrane that divides the cell in two.

Science Practice Connection for AP® Courses

Activity

Use a set of pipe cleaners (or other materials as directed by your teacher) that you can use to model chromosomes during mitosis and meiosis:
1. Each of the pipe cleaners represents a single, unreplicated chromosome. Each chromosome should differ in size, as they do in most organisms. Assume that your dividing cell contains three chromosomes: numbered chromosome 1, 2, and 3.
2. Using both members of each homologous pair for chromosomes 1–3, model how the chromosomes would appear in a cell that had just finished the S phase of the cell cycle. Once your teacher has approved your model, have one member of your group document the model by photographing or drawing it.
3. Now, repeat step 2 but show the cell at metaphase during mitosis.
4. Finally, model the two daughter cells that will result from mitosis. Again, have one member of your group document the model.
5. Repeat steps 2–5 for both meiosis I and meiosis II. Remember that you should have four daughter cells at the end of meiosis II. Also remember to ask your teacher for approval and document your model before moving on to the next phase of meiosis.
6. Exchange/copy all of the drawings or photographs that your group took of your models. As a group or individually (as directed by your teacher) create a report to turn in that labels and explain each picture of your model.
An organism’s ploidy count is the total number of chromosome sets contained in each body cell. Most organisms have a ploidy level of 2, meaning that they have two sets of chromosomes due to presence of homologous pairs. However, some plants are multiploid, meaning they can have ploidy levels greater than 2. The table shows possible multiploid levels of some common crop plants.


Common name	Multiploid chromosome count	Normal chromosome count
Bananas	33	11
Potatoes	48	12
Wheat	42	7
Sugar cane	80	10

Analyze the data with a partner of in a group as directed by your teacher. On a separate sheet of paper, answer the following questions.

How does the multiploid count of the crop plants relate to their normal chromosome count?
Explain the basis for the relationship you described in part a, in terms of what occurs to chromosomes during replication and meiosis.
Give one additional example of a possible multiploid chromosome count for each species in the table above.

Exercise 1

A. A comparison of the relative time intervals of mitotic stages can be made by completing the task described. In evaluating each time interval, the problem suggests that you assume that the length of time to complete one cell cycle is 24 hours. How can that assumption be tested?

Suppose that you have a growth chamber in which roots of a newly germinated plant can be examined visually with a lens that provides a magnification from which lengths can be determined with a precision of ± 0.05 mm. The field of view can be rotated so that measurements can be made of both the length and diameter of the growing tip. A large number of growing roots can be studied. Tips can be sampled, sectioned, and examined microscopically with a 25× magnification so that estimates of the diameter and length of cells can be made.

Cells in the growing tip of the root rapidly undergo mitosis, just as the whitefish blastula described in Figure 10.11. With increasing distance from the growing tip, the rate at which mitosis occurs slows until tissue is reached in which the initiation of the cell cycle is delayed.

A. Describe a sequence of measurements that could be used to test the assumption that the cell cycle, once started, has a total time interval of 24 hours. Hint: Rather than counting cells, it might be useful to measure the length of the root tip and the average length of a cell.

B. Using the data obtained from your measurements described in part A, how can the rate of cell division be calculated?

An experiment that is perhaps similar to one you have proposed was conducted previously (Beemster and Baxter, 1998), and the results are shown in the table.

Distance (mm)	Per hour
0	0.035 ± 0.01
0.1	0.047 ± 0.005
0.2	0.044 ± 0.01
0.3	0.039 ± 0.01
0.4	0.042 ± 0.01
0.5	0.031 ± 0.005

Table 10.1

C. Using these data, estimate the length of time of the cell cycle, including an estimate of precision by calculating the standard deviation.

Growth factors are signals that initiate cell division in eukaryotes. (The data in the table above show that cells in the plant root less than a mm from the root tip are showing a reduction of growth rate.) The interaction of two plant hormones, auxin and brassinosteroids, have been shown [Chaiwanon and Wang, Cell, 164(6), 1257, 2016] to regulate cell division in root tips. Auxin concentrations are higher near the root tip and decrease with distance from the tip. Brassinosteroids decrease in concentration near the root tip. Auxin is actively transported between cells, whereas brassinosteroids have limited transport between cells.

D. Based on these data and the observed distribution of brassinosteroids and auxin in the growing root, predict a mechanism for their interaction and justify the claim that brassinosteroid synthesis is negatively regulated by auxin transported to the cell, and that auxin is positively regulated and amplified.

Think About It

Chemotherapy drugs such as vincristine and colchicines disrupt mitosis by binding to tubulin (the subunit of microtubules) and interfering with microtubule assembly and disassembly. What mitotic structure is targeted by these drugs, and what effect would this have on cell division?

G0 Phase

G₀Phase

Not all cells adhere to the classic cell cycle pattern in which a newly formed daughter cell immediately enters the preparatory phases of interphase, closely followed by the mitotic phase. 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.

Scientific Method Connection

Determine the Time Spent in Cell Cycle Stages

Problem: How long does a cell spend in interphase compared to each stage of mitosis?

Background: A prepared microscope slide of blastula cross-sections will show cells arrested in various stages of the cell cycle. It is not visually possible to separate the stages of interphase from each other, but the mitotic stages are readily identifiable. If 100 cells are examined, the number of cells in each identifiable cell cycle stage will give an estimate of the time it takes for the cell to complete that stage.

Problem Statement: Given the events included in all of interphase and those that take place in each stage of mitosis, estimate the length of each stage based on a 24-hour cell cycle. Before proceeding, state your hypothesis.

Test your hypothesis: Test your hypothesis by doing the following:

Place a fixed and stained microscope slide of whitefish blastula cross-sections under the scanning objective of a light microscope.
Locate and focus on one of the sections using the scanning objective of your microscope. Notice that the section is a circle composed of dozens of closely packed individual cells.
Switch to the low-power objective and refocus. With this objective, individual cells are visible.
Switch to the high-power objective and slowly move the slide left to right, and up and down to view all the cells in the section (Figure 10.11). As you scan, you will notice that most of the cells are not undergoing mitosis but are in the interphase period of the cell cycle.

Figure 10.11 Slowly scan whitefish blastula cells with the high-power objective as illustrated in image (a) to identify their mitotic stage. (b) A microscopic image of the scanned cells is shown. (credit micrograph: modification of work by Linda Flora; scale-bar data from Matt Russell)
Practice identifying the various stages of the cell cycle, using the drawings of the stages as a guide (Figure 10.8).
Once you are confident about your identification, begin to record the stage of each cell you encounter as you scan left to right, and top to bottom across the blastula section.
Keep a tally of your observations and stop when you reach 100 cells identified.
The larger the sample size (total number of cells counted), the more accurate the results. If possible, gather and record group data prior to calculating percentages and making estimates.

Record your observations: Make a table similar to Table 10.2 in which you record your observations.

Results of Cell Stage Identification
Phase or Stage	Individual Totals	Group Totals	Percent
Interphase
Prophase
Metaphase
Anaphase
Telophase
Cytokinesis
Totals	100	100	100 percent

Table 10.2

Analyze your data/report your results: To find the length of time whitefish blastula cells spend in each stage, multiply the percent (recorded as a decimal) by 24 hours. Make a table similar to Table 10.3 to illustrate your data.

Estimate of Cell Stage Length
Phase or Stage	Percent (as Decimal)	Time in Hours
Interphase
Prophase
Metaphase
Anaphase
Telophase
Cytokinesis

Table 10.3

Disclaimer

This section may include links to websites that contain links to articles on unrelated topics. See the preface for more information.

10.2 The Cell Cycle

Learning Objectives