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CHAPTER 12THE CELL CYCLE

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I. OVERVIEW1. Cell division is defined as the reproduction of cells and is the

characteristic that best distinguishes living things from nonliving matter.2. In unicellular organisms, cell division reproduces an entire

organism (Ex: bacteria)3. In multicellular organisms, cell division functions in:

Development from a fertilized egg Growth Repair

4. Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division.

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Unicellular Reproduction

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5. Cell division involves:a. Precise replication of DNAb. Movement of this DNA to opposite ends of the cellc. Separation into two daughter cells with identical

genetic information, DNA

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II. Concept 12.1: Cell division results in genetically identical daughter cells

A. Cellular Organization of the Genetic Material1. All the DNA in a cell constitutes the cell’s genome2. A genome can consist of a single DNA molecule (common

in prokaryotic cells) or a number of DNA molecules (common in eukaryotic cells)

3. DNA molecules in a cell are packaged into chromosomes4. Every eukaryotic species has a characteristic number of

chromosomes in each cell nucleus (humans-46)

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5.Somatic cells (nonreproductive cells) have two sets of chromosomes; produced by mitosis; genetically identical

6.Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells; produced by meiosis; genetically unique

7.Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division, present in this state when cell is not dividing

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Eukaryotic Chromosome

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B. Distribution of Chromosomes During Eukaryotic Cell Division1. In preparation for cell division, DNA is replicated and the

chromosomes condense2.Each duplicated chromosome has two sister chromatids, which

separate during cell division3.The centromere is the narrow “waist” of the duplicated chromosome,

where the two chromatids are most closely attached4.Chromatin

Active form of DNA found in a non-dividing cell DNA—genetic material Proteins—help maintain chromosomal structure and help control

gene activity

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Doubled Chromosome chromatid

centromerekinetochore

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5. Eukaryotic cell division consists of:Mitosis—the division of the nucleusCytokinesis—the division of the cytoplasm

6. Gametes are produced by a variation of cell division called meiosis

7. Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell

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III. Concept 12.2: The Cell Cycle In 1882, the German anatomist Walther Flemming

developed dyes to observe chromosomes during mitosis and cytokinesis

A. Phases of the Cell Cycle1.The cell cycle consists of:

Mitotic (M) phase (mitosis and cytokinesis)Interphase (cell growth and copying of chromosomes in preparation for cell division)

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2. Interphase (about 90% of the cell cycle) can be divided into subphases:

a. G1 Phase (first gap)—cell grows; first growth phase when the centrioles replicate

b. S Phase (synthesis)--DNA replicatesc. G2 Phase (second gap)—cell grows; second

growth phase during which the cell is preparing for mitosis by producing proteins, ATP, etc.3. The cell grows during all three phases, but

chromosomes are duplicated only during the S phase

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Cell Cycle

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B. G2 of Interphase Nucleus well defined and bound by nuclear

envelope One or more nucleoli present Two pairs of centrioles adjacent to nucleus Around each pair of centrioles are

microtubules that form a radial array called an aster (animal cells only)

Chromosomes have duplicated and appear as chromatin

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C. Actual Stages of Mitosis Are:ProphasePrometaphaseMetaphaseAnaphaseTelophase

D. Prophase1. Changes in nucleus:

Nucleoli disappearChromatin fibers become tightly coiled and folded to form

observable chromosomes

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2. Changes in cytoplasm Mitotic spindle forms

--Composed of microtubules and associated proteins which are arranged between the two centrosomes (microtubule-organizing center)

Centrosomes move apart--Apparently they are propelled along the surface of the nucleus by lengthening of microtubule bundles between them

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B. Prometaphase1. Nuclear envelope fragments2. Microtubules interact with chromosomes3. Spindle fibers (bundles of microtubules) extend

from each pole toward the equator (midpoint between the poles) (aka metaphase plate) of the cell4. Each chromatid has a kinetochore (specialized

structure located at the centromere region)5. Bundles of microtubules (kinetochore microtubules) attach to kinetochores and put chromosomes into agitated motion6. Microtubules (nonkinetochore microtubules) radiated from each centrosome toward the metaphase plate (equator) without attaching to chromosome

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C. Metaphase1. Centrosomes positioned at poles (opposite

ends ) of the cell2. Chromosomes move to metaphase plate (plane equidistant between the spindle poles)

3. Centromeres of all chromosomes aligned on metaphase plate4. Kinetochore fibers of sister chromatids face opposite

poles so identical chromatids are attached to kinetochore fibers radiating from opposite ends of the parent cell

5. Entire structure formed by nonkinetochore microtubules plus kinetochore microtubules called the spindle

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D. Anaphase1. Begins when paired centromeres of each chromosome

move apart2. Sister chromatids separate and are considered

chromosomes3. Spindle apparatus starts moving the separate chromosomes

toward opposite poles4. Chromosomes move in a V-shape because of attachment of

kinetochore fibers to centromere5. Kinetochore microtubules shorten at end attached to

kinetochores6. Poles of cell move farther apart slightly elongating the cell

7. At end of phase two poles have complete and equivalent collections of chromosomes

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E. Telophase1. Nonkinetochore microtubules further elongate the cell2. Daughter nuclei begin to form at the two poles3. Nuclear envelop reforms from fragments of parent cell nuclear

envelope and other portions of endomembrane system4. Nucleoli reappear5. Chromosomes uncoil and appear as chromatin6. Cytokinesis occurs7. At the end of the phase:

Mitosis is complete Cytokinesis has begun and the appearance of two separate

daughters cells occurs shortly after mitosis is complete

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Animal Mitosis

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Plant Mitosis

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Animal Cell

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Plant Cell

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F. Mitotic Spindle

1.Important to events occurring in mitosis2.Forms in cytoplasm during prophase3.Composed of microtubules and associated proteins4.Elements come from partial disassembly of the cytoskeleton5. Elongation occurs by the addition of tubulin (protein) subunits

at one end6.Assembly begins in the centrosome (microtubule organizing

center).7.In animal cells, a pair of centrioles is in the center of the

centrosome.

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8. F(x) of centrioles is undefined.9. Parallel microtubules form bundles called spindle fibers.

10. Fibers elongate or shorten by adding and removing tubulin subunits from end away from centrosome.

11. 2 Types of Spindle Fibers: a. kinetochore microtubules

Attached to kinetochoreF(x): -arrange chromosomes so kinetochores face the

poles-align chromosomes at cell’s midline

-to move chromosomes to poles

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b. nonkinetochore microtubules Are not attached to kinetochore Overlap at center of cell F(x): elongate whole cell during anaphase Movement requires ATP

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Spindle Fibers

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Kinetochore Microtubule Depolymerization

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G. Cytokinesis

1. Process of cytoplasmic division that follows mitosis2. Begins in telophase3. Differs in plant and animal cells4. Animal Cells

Occurs as cleavageCleavage furrow forms as a shallow groove on cell surface

near metaphase plate (in animal cells only)Contractile ring of actin and myosin microfilaments forms on

cytoplasmic side of furrowMicrofilaments contract until parent cell is pinched in two

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5. Plant CellsCell plate forms across midline of parent cell (equator)Cell plate forms from fusing vesicles derived from Golgi

apparatus that have moved along microtubules to cell’s center

Cell plate enlarges until its surrounding membrane fuses with the existing plasma membrane

New cell wall forms between two membranes from contents of cell plate

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Cytokinesis

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G. Binary Fission

1. Cells grow to double their size and divide to form two cells2. Prokaryotes (bacteria and cyanobacteria) reproduce by binary

fission (division in half).3. Have a single circular DNA molecule that carries most of the genes4. Soon after chromosome replication begins, one copy of the

origin of replication (first replicated region) begins to move toward the other end of the cell.

5. Replication continues and eventually one copy of the origin is at each end of the cell.

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5. Replication finishes.

6. Plasma membrane grows inward, and new cell wall is deposited.

7. Two daughter cells

8. Single celled eukaryotes must still go through mitosis prior to division.

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H. The Evolution of Mitosis Since prokaryotes evolved before eukaryotes, mitosis probably

evolved from binary fission Certain protists exhibit types of cell division that seem

intermediate between binary fission and mitosis

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VI. Concept 12.3: Regulation of the Cell CycleNormal growth, development and maintenance of a cell depends on the timing and rate of mitosis.

The frequency of cell division varies with the type of cell-human skin cells divide frequently-liver cells divide to repair damaged cells-nerve, muscle, and other specialized cells do not divide in mature humans

These cell cycle differences result from regulation at the molecular level

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A. Cell Cycle Control System1.Cell cycle appears to be driven by specific chemical

signals in the cytoplasm.2. The sequential events of the cell cycle are directed by a

distinct cell cycle control system, which is similar to a clock

3. The cell cycle control system is regulated by both internal and external controls

4. The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received

5. When the control system malfunctions, cancer may result.

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Cell Cycle Checkpoints

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6. Checkpoints:Stop and go signals that regulate the cell cycleReport status of cellular conditionsIntegrate internal (intracellular) and external (extracellular) information

7. For many cells, the G1 checkpoint seems to be the most important one

If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide

If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase

-Ex: a. muscle and nerve cells until deathb. liver cells until recruited back to cell cycle by such cues as growth factors

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B. Cyclins and Cyclin-Dependent Kinases

1. Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks) During interphase levels of cyclins rise, then fall abruptly during mitosisKinases catalyze the transfer of Pi group from ATP to a target protein and synchronize the ordered sequence of cell cycle events Protein kinases - provide go ahead signals of G1 and G2 checkpoints

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B. Cyclins and Cyclin-Dependent Kinases

2. The activity of cyclins and Cdks fluctuates during the cell cycle* cyclins – proteins that bind to and activate protein kinase

3. MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G2 checkpoint into the M phase

Cyclins + Cdk = MPF (maturation promoting factor) MPF activity is directly proportional to the concentration of cyclins.

Concentration/Activity rises during S and G2 phases and falls during M phase. MPF phosphorylates many proteins, initiating mitosis.

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G2 Checkpoint

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C. Stop and Go Signs: Internal and External Signals at the Checkpoints

1. An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase

2. Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divideFor example, platelet-derived growth factor (PDGF)

stimulates the division of human fibroblast cells in culture3. Another example of external signals is density-dependent

inhibition, in which crowded cells stop dividing4. Most animal cells also exhibit anchorage dependence, in

which they must be attached to a substratum in order to divide

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PDGF

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Density-dependent Inhibition

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D. Cancer Cells (abnormal cells)1. Cancer cells do not respond normally to the body’s control

mechanisms2. Cancer cells may not need growth factors to grow and divide:

They may make their own growth factorThey may convey a growth factor’s signal without the

presence of the growth factorThey may have an abnormal cell cycle control system

3. A normal cell is converted to a cancerous cell by a process called transformation

4. Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue

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5. If abnormal cells remain at the original site, the lump is called a benign tumor

6. Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form secondary tumors

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Breast Cancer

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Plant Mitosis

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You should now be able to:

1. Describe the structural organization of the prokaryotic genome and the eukaryotic genome

2. List the phases of the cell cycle; describe the sequence of events during each phase

3. List the phases of mitosis and describe the events characteristic of each phase

4. Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules, nonkinetochore microtubules, and asters

5. Compare cytokinesis in animals and plants

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6. Describe the process of binary fission in bacteria and explain how eukaryotic mitosis may have evolved from binary fission

7. Explain how the abnormal cell division of cancerous cells escapes normal cell cycle controls

8. Distinguish between benign, malignant, and metastatic tumors

Exit Slip How many chromatids are in a duplicated chromosome? A chicken has 78 chromosomes in its somatic cells.

How many chromosomes did the chicken inherit from each parent? How many chromosomes are in each of the chicken’s gametes? How many chromosomes will be in each somatic cell of the

chicken’s offspring?