1. The Cell Cycle
Chapter 12

2. What Cellular Reproduction Accomplishes
The key roles of cellular division:
The passing on of genes from cell to cell
The reproduction of organisms
The continuity of life is based on the reproduction of cells, or cellular division

4. Types of Cellular Reproduction
Unicellular organisms
Reproduce by cell division
Multicellular organisms depend on cell division for:
Development from a fertilized cell
Growth
Repair
For example dividing cells in your bone marrow.

5. 100 µm
(a) Reproduction. An amoeba, a single-celled eukaryote, is dividing into two cells. Each new cell will be an individual organism (LM).
20 µm
200 µm
(b) Growth and development This micrograph shows a sand dollar embryo shortly after the fertilized egg divided, forming two cells (LM).
(c) Tissue renewal. These dividing bone marrow cells (arrow) will give rise to new blood cells (LM).

6. Ordinarily cell division produces two daughter cells that are genetically identical. Name three functions of this type of cell division.

7. Cellular Organization of the Genetic Material
A cell’s endowment of DNA, its genetic information is called its genome
The DNA molecules in a cell are packaged into chromosomes
Eukaryotic chromosomes consist of Chromatin, a complex of DNA and protein that condenses during cell division
In animals Somatic Cells have two sets of chromosomes and Gametes have one set of chromosomes
Chromosome named because they can take up dyes used in microscopy: “chroma” color: “soma”: body

8. Distribution of Chromosomes During Cell Division
In preparation for cell division DNA is replicated and the chromosomes condense
Each duplicated chromosome has two sister chromatids, which separate during cell division
Sister chromatids, each containing an identical DNA molecule

9. Separation of sister chromatids
Chromosome duplication (including DNA synthesis)
Centromere
Separation of sister chromatids
Sister chromatids
Centromeres
A eukaryotic cell has multiple chromosomes, one of which is represented here. Before duplication, each chromosome has a single DNA molecule.
Once duplicated, a chromosome consists of two sister chromatids connected at the centromere. Each chromatid contains a copy of the DNA molecule.
Mechanical processes separate the sister chromatids into two chromosomes and distribute them to two daughter cells.
Figure 12.4

10. Comparison of Cell Division
Eukaryotic cell division consists of:
Mitosis, the division of the nucleus
Cytokinesis, the division of the cytoplasm
In Meiosis:
Gametes are produced after a reduction in chromosome number

11. Phases of the Cell Cycle
The cell cycle consists of the mitotic phase alternating with interphase
INTERPHASE G1
S (DNA synthesis) G2
Cytokinesis Mitosis
MITOTIC (M) PHASE

12. Interphase
Mitosis and cytokinesis are usually the shortest part of the cell cycle.
They alternate with interphase that accounts for roughly 90% of the cycle.
The cell grows and copies its chromosomes in preparation for cell division
Interphase can be divided into subphases
G1 phase
S phase
G2 phase
G1: First gap: Grows
S: Synthesis: Chromosomes are duplicated
G2: Second gap: Prepares for cell division

13. Mitosis Consists of Five Distinct Phases
Prophase
Prometaphase
Metaphase
Anaphase
Telophase

14. Bell-Ringer
During which stages of the cell cycle would a chromosome consist of two identical chromosomes?
From the end of the S phase in Interphase to the middle of metaphase of mitosis.

15. Kinetochore microtubule
G2 OF INTERPHASE
PROPHASE
PROMETAPHASE
Centrosomes (with centriole pairs)
Chromatin (duplicated)
Early mitotic spindle
Aster
Centromere
Fragments of nuclear envelope
Kinetochore
Nucleolus
Nuclear envelope
Plasma membrane
Chromosome, consisting of two sister chromatids
Kinetochore microtubule
Nonkinetochore microtubules

16. TELOPHASE AND CYTOKINESIS
Centrosome at one spindle pole
Daughter chromosomes
METAPHASE
ANAPHASE
TELOPHASE AND CYTOKINESIS
Spindle
Metaphase plate
Nucleolus forming
Cleavage furrow
Nuclear envelope forming

17. The Mitotic Spindle: A Closer Look
The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis
The spindle arises from the centrosomes and includes spindle microtubules and asters
Some spindle microtubules attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate

18. Centrosome Aster Chromosomes Microtubules 0.5 µm 1 µm
Sister chromatids
Metaphase Plate
Kinetochores
Overlapping nonkinetochore microtubules
Kinetochores microtubules
Chromosomes
Microtubules
0.5 µm
1 µm

19. Anaphase In anaphase, sister chromatids separate
Move along the kinetochore microtubules toward opposite ends of the cell
Nonkinetechore microtubules from opposite poles
Overlap and push against each other, elongating the cell
Commences suddenly when proteins holding together the sister chromatids of each chromosome are inactivated.
How do the kinetochore microtubules function in this poleward movement of chromosomes?

20. Kinetochore Spindle pole EXPERIMENT
1 The microtubules of a cell in early anaphase were labeled with a fluorescent dye that glows in the microscope (yellow).
Spindle pole
Kinetochore
The primary mechanism of movement involves motor proteins on the kinetochores that “walk” a chromosome along the attached microtubules toward the nearest pole. Meanwhile, the microtubules shorten by depolymerizing at their kinetochore ends, releasing tubulin subunits.

21. Telophase In telophase
Genetically identical daughter nuclei form at opposite ends of the cell
Daughter nuclei begin to form
Nuclear envelopes arise from the fragments of the parent cell’s nuclear envelope and other portions of the endomembrane system.

22. Cytokinesis: Animal Cells
In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow.
Cleavage furrow
Contractile ring of microfilaments
Daughter cells
100 µm
A cleavage furrow is a shallow groove in the cell surface near the old metaphase plate. On the cytoplasmic side, the furrow is a contractile ring of actin microfilaments associated with molecules of the protein myosin. The actin and the myosin components interact causing the ring to contract. Like the “pulling of a drawstring”.

23. Cytokinesis: Plant Cells
Daughter cells
1 µm
Vesicles forming cell plate
Wall of patent cell
Cell plate
New cell wall
(b) Cell plate formation in a plant cell (SEM)
In plant cells, during cytokinesis a cell plate forms.
During telophase, vesicles derived from the Golgi Apparatus move along the microtubules to the middle of the cell, where they coalesce, producing a cell plate. Cell Wall materials carried in the vesicles collect in the cell plate as it grows. The cell plate enlarges until its surrounding membrane fuses with the plasma membrane along the perimeter of the cell.

24. Mitosis in Plants Chromatine condensing Nucleus Chromosome Nucleolus 1
Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is staring to from.
Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelop will fragment.
Metaphase. The spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate.
Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of cell as their kinetochore microtubles shorten.
Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divided the cytoplasm in two, is growing toward the perimeter of the parent cell. 2 3 4 5
Nucleus
Nucleolus
Chromosome
Chromatine condensing

25. Binary Fission Prokaryotes (bacteria)
Reproduce by a type of cell division called Binary Fission
In binary fission
The bacterial chromosome replicates
The two daughter chromosomes actively
move apart
In bacteria, most genes are carried on a single bacterial chromosome that consists of a circular DNA molecule and associated proteins.

26. Origin of
replication
E. coli cell
Bacterial
Chromosome
Cell wall
Plasma
Membrane
Two copies
of origin
Origin
Origin of Replication: site where the replication of a DNA molecule begins
Chromosome replication begins.
Origins of Replication move to opposite ends of the bacterial cell.
Replication finishes and the plasma membrane grows inward. The new cell is deposited.
Two daughter cells result.

27. The Evolution of Mitosis
Since prokaryotes preceded eukaryotes by billions of years
It is likely that mitosis evolved from bacterial cell division
Certain protists
Exhibit types of cell division that seem intermediate between binary fission and mitosis carried out by most eukaryotic cells

28. Molecular Control System
The cell cycle is regulated by a molecular control system
The timing and rate of cell division in different plants or animals are crucial to normal growth
The frequency of cell division varies with the type of cell
These cell cycle differences result from regulation at the molecular level
Molecules present in the cytoplasm regulate progress through the cell cycle
Skin cells divide frequently. Liver cells possess the ability to but chose whether to or not… saving up for emergencies. Neurons may never divide in an adult’s lifetime.

29. S M G1 EXPERIMENTS RESULTS
In each experiment, cultured mammalian cells at two different phases of the cell cycle were induced to fuse.
When a cell in the M phase was fused with a cell in G1, the G1 cell immediately began mitosis— a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.
EXPERIMENTS
RESULTS
CONCLUSION
The results of fusing cells at two different phases of the cell cycle suggest that molecules present in the cytoplasm of cells in the S or M phase control the progression of phases.
When a cell in the S phase was fused with a cell in G1, the G1 cell immediately entered the S phase—DNA was synthesized. S M G1
Experiment 1
Experiment 2
The results of fusing cells at two different phases of the cell cycle suggest that molecules present in the cytoplasm of cells in the S or M phase control the progression of phases.

30. The Cell Cycle Control System
The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock
Control system
G2 checkpoint
M checkpoint
G1 checkpoint G1 S G2 M
Internal control and external adjustment, the cell cycle is regulated at certain checkpoints by both internal and external controls.
Checkpoint: critical point where stop and go-ahead signals can regulate the cycle. (The signals are transmitted by the signal transduction pathways discussed in Chapter 11.)
G1 Checkpoint is the most important, if it passes this checkpoint the cell normally moves on to S, G2, and to division. If it does not receive the green light, it will exit the cycle, switching into a non-dividing state called G0 phase. (This is where most of our cells reside.)

31. G1 checkpoint G1 G0
(a) If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues      on in the cell cycle.
(b) If a cell does not receive a go-ahead signal at the G1checkpoint, the cell exits the cell cycle and goes into G0, a
nondividing state.

32. The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases
The clock has specific checkpoints
Where the cell cycle stops until a go-ahead signal is received
Two types of regulatory proteins are involved in cell cycle control
Cyclins and Cyclin-Dependent Kinases (Cdks)
The activity of cyclins and Cdks fluctuates during the cell cycle
Protein kinases are enzymes that activate other proteins by phosphorylating them. Particular protein kinases give the go-ahead signal at the G1 and G2 checkpoints.
To be considered “active” the kinase must be bound to a cyclin, a protein whose concentration is in a state of constant fluctuation.
These kinases are referred to as cyclin-dependent kinases, or Cdks. The presence of the Cdk rises and falls with the concentration of cyclin.
Cyclin accumulates (during G2) and associated with Cdk molecules, the resulting MPF (maturing-promoting factor) initiates mitosis, by phosphorylating a variety of proteins. MPF acts as a kinase directly and indirectly by activating other kinases.
During anaphase, MPF helps switch itself off by initiating a process that leads to the destruction of its own cyclin.

33. During G1, conditions in the cell favor degradation
of cyclin, and the Cdk component of MPF is recycled. 5
During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G1 phase. 4
Accumulated cyclin molecules
combine with recycled Cdk mol-
ecules, producing enough molecules of MPF to pass the G2 checkpoint and initiate the events of mitosis. 2
Synthesis of cyclin begins in late S phase and continues through G2. Because cyclin is protected from degradation during this stage, it accumulates. 1
Cdk
G2 checkpoint
Cyclin
MPF
Cyclin is degraded
Degraded Cyclin G1 G2 S M
MPF activity
Time
(a) Fluctuation of MPF activity and cyclin concentration during
the cell cycle
(b) Molecular mechanisms that help regulate the cell cycle
MPF promotes mitosis by phosphorylating various proteins. MPF‘s activity peaks during metaphase. 3

34. Stop and Go Signs: Internal and External Signals at the Checkpoints
Both internal and external signals control the cell cycle checkpoints
Growth factors stimulate other cells to divide
In density-dependent inhibition
Crowded cells stop dividing
Most animal cells exhibit anchorage dependence
In which they must be attached to a substratum to divide
Growth factor is a protein released by certain cells that stimulates other cells to divide.

35. Cancer Cells
Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence
Do not respond normally to the body’s control mechanisms and cause the formation of tumors
Malignant tumors invade surrounding tissues and can metastasize
Exporting cancer cells to other parts of the body where they may form secondary tumors

36. Tumor
Glandular
tissue
Cancer cell
Blood vessel
Lymph vessel
Metastatic Tumor