1. Key Concepts
In eukaryotes, most dividing cells go through a cycle that consists of four phases.
After chromosomes are copied during S phase, they are moved to the middle of the cell during M phase (mitosis). One chromosome copy is distributed to each of two daughter cells. Mitosis and cytokinesis produce two cells that are genetically identical to the parent cell.

2. Key Concepts
Progression through the cell cycle is carefully controlled.
In multicellular organisms, uncontrolled cell division may lead to cancer. Different types of cancer result from different types of defects in control over the cell cycle.

3. Introduction to Cell Division
Cells arise through the division of preexisting cells. There are two types of cell division: meiosis and mitosis.
Both forms of cell division are usually accompanied by cytokinesis, in which the cytoplasm of the cell divides into two distinct daughter cells.

4. Contrasting Mitosis and Meiosis
Meiosis leads to the production of gametes (eggs and sperm).
Daughter cells have half the amount of genetic material as the parent cell.
Mitosis leads to the production of all other cell types, referred to as somatic cells.
Genetic material is copied and then divided equally.
Daughter cells are genetically identical to the parent cell.

5. Functions of Mitosis
Mitosis and cytokinesis are responsible for three key events in multicellular eukaryotes:
Growth
Wound repair
Asexual reproduction

6. What Is a Chromosome?
Chromosomes contain a single long double helix of deoxyribonucleic acid (DNA) wrapped around proteins.
DNA encodes the cell’s genetic information.
A gene is a section of DNA that encodes a specific protein or RNA.
Chromosomes can be stained with dyes and observed under the light microscope.

8. Chromosomes Change before and during Mitosis
The purpose of mitosis is to distribute chromosomes to daughter cells during cell division.
To this end, each chromosome is replicated prior to mitosis.
As mitosis starts, the chromosomes condense from long, thin filaments into compact structures that can be moved around the cell efficiently.
At the end of mitosis, one of the chromosome copies is distributed to each of two daughter cells.

9. Chromosome Replication
Prior to mitosis, each chromosome is replicated.
Each of the DNA copies in a replicated chromosome is called a chromatid.
Chromatids are joined together along their entire length as well as at a specialized region of the chromosome called the centromere.
Chromatids from the same chromosome are referred to as sister chromatids.
Even though a replicated chromosome consists of two chromatids, it is still considered a single chromosome.

11. M Phase and Interphase
Growing cells cycle between a dividing phase called the mitotic (M) phase and a nondividing phase called interphase.

12. Interphase – S Phase
The cell cycle is the orderly sequence of events that occurs from the formation of a eukaryotic cell through the duplication of its chromosomes to the time it undergoes cell division.
A visualization technique called autoradiography allowed researchers to identify the part of the cell cycle during which DNA replication occurs.
Chromosome replication occurs only during interphase and not during M phase.
The stage in which DNA replication occurs is called the synthesis (S) phase.

13. Interphase – Gap Phases
Interphase also includes two gap phases, during which no DNA synthesis occurs.
The first gap, G1 phase, occurs before the S phase.
The second gap, G2 phase, occurs between S phase and mitosis.
During the gap phases, organelles replicate and additional cytoplasm is made in preparation for cell division.
It takes a cell about 24 hours to complete one cell cycle.
G1 phase lasts 7–9 hours.
S phase lasts 6–8 hours.
G2 phase lasts 4–5 hours.

14. The Cell Cycle
There are a total of four phases in the cell cycle: M phase and an interphase consisting of the G1, S, and G2 phases.
Gap phases allow the cell to grow large enough and synthesize enough organelles to ensure the daughter cells will be normal in size and function.

16. Mitosis Overview
Mitosis results in the division of replicated chromosomes and formation of two daughter nuclei with identical chromosomes and genes.
Mitosis is usually accompanied by cytokinesis.
Every species has a characteristic number of chromosomes.
Humans have 46.

17. Chromosomes Change during the Cell Cycle
Eukaryotic chromosomes consist of DNA associated with histone proteins.
In eukaryotes this DNA-protein material is called chromatin.
During interphase, most chromatin is “relaxed” or uncondensed, forming long, threadlike strands.
After replication during S phase, each chromosome consists of two genetically identical sister chromatids attached at the centromere.
At the start of mitosis the replicated chromosomes condense.

18. Events in Mitosis
During mitosis, the two sister chromatids separate to form independent chromosomes, and one copy of each chromosome goes to each of the two daughter cells. As a result, each daughter cell receives a copy of the genetic information that is contained in each chromosome.
Mitosis (M phase) is a continuous process with five subphases based on specific events:
Prophase
Prometaphase
Metaphase
Anaphase
Telophase

20. Prophase
During prophase, chromosomes condense and first become visible in the light microscope.
The mitotic spindle, if made up of microtubules called spindle fibers, forms from a microtubule-organizing center.
Polar microtubules push the poles of the cell away from each other during mitosis.
Kinetochore microtubules pull chromosomes to the poles of the cell during mitosis.
In animal cells, the microtubule-organizing center is a centrosome—a structure that contains a pair of centrioles.

21. Prometaphase During prometaphase: The nuclear envelope breaks down.
The nucleolus disappears.
Kinetochore microtubules from each mitotic spindle attach to one of the sister chromatids of each chromosome.
Attachment occurs in the centromere region at the kinetochore.

22. Metaphase
During metaphase, the formation of the mitotic spindle is completed.
Motor proteins on the kinetochore microtubules pull each chromosome in opposite directions, causing the chromosomes to line up in the middle of the cell.
The imaginary plane formed by this is called the metaphase plate.

23. Anaphase
During anaphase, centromeres split and sister chromatids are pulled by the spindle fibers toward opposite poles of the cell.
Replicated chromosomes split into two identical sets of unreplicated chromosomes.
As soon as they are no longer attached at the centromere, sister chromatids become daughter chromosomes.
In addition, motor proteins of the polar microtubules push the two poles of the cell away from each other.

24. Telophase During telophase:
A new nuclear envelope begins to form around each set of chromosomes.
The mitotic spindle disintegrates.
The chromosomes begin to de-condense.
When two independent nuclei have formed, mitosis is complete.

26. 26

27. Cytokinesis
Cytokinesis typically occurs immediately after mitosis. During this process, the cytoplasm divides to form two daughter cells, each with its own nucleus and complete set of organelles.

28. Different Cell Types Undergo Cytokinesis Differently
Cytokinesis in plants occurs as vesicles are transported from the Golgi apparatus to the middle of the dividing cell. These vesicles fuse to form a cell plate.
Cytokinesis in animals, fungi, and slime molds occurs when a ring of actin and myosin filaments contracts inside the cell membrane, causing it to pinch inward in a cleavage furrow.
Bacteria do not undergo cytokinesis, but instead divide via fission, a process similar to animal cytokinesis.

31. How Do Chromosomes Move during Mitosis?
Kinetochore microtubules remain stationary during anaphase; they shorten because tubulin subunits of the microtubules are lost from their plus ends at the kinetochore.
Dyneins and other kinetochore motor proteins are attached to the kinetochore’s fibrous crown and “walk” toward the minus end of the spindle fiber.
As the microtubule shortens and the detach-move-reattach cycle of the motor proteins repeats, the chromosome is pulled to one end of the mitotic spindle.

34. Control of the Cell Cycle
Cell-cycle length can vary greatly among cell types; variation in the length of G1 phase is responsible for these differences.
G1 phase is essentially eliminated in rapidly dividing cells.
Nondividing cells get permanently stuck in G1 phase; this arrested stage is called the G0 state.
The rate of cell division can also respond to changes in environmental conditions.
These variations in cell-cycle length suggest that the cell cycle is regulated and that regulation varies among cells and organisms.

35. Mitosis-Promoting Factor Induces Mitosis
Mitosis-promoting factor (MPF) is present in the cytoplasm of M-phase cells and induces mitosis in all eukaryotes.
MPF is composed of two distinct subunits: a protein kinase and a cyclin.
The protein kinase is an enzyme that catalyzes the transfer of a phosphate group from ATP to a target protein (phosphorylation).
The cyclin subunit functions as a regulatory protein.

36. Cyclin Concentration Regulates MPF Concentration
The concentration of MPF cyclin increases during interphase, then peaks in M phase before decreasing again.
The MPF protein kinase is a cyclin-dependent kinase (Cdk) that is active only when bound to the cyclin subunit. Thus, when cyclin concentrations are high, more MPF is active and the target proteins are phosphorylated, initiating mitosis.

38. MPF Activation
After it binds to cyclin, MPF’s Cdk subunit becomes phosphorylated at two sites, rendering it inactive.
Late in G2 phase enzymes cause one of the phosphate groups on the Cdk subunit to drop off.
This dephosphorylation reaction changes MPF’s shape, activating it.
Once MPF is activated, it triggers a chain of events, culminating in the condensation of chromosomes and formation of the mitotic spindle apparatus.

39. MPF Deactivation
During anaphase, an enzyme complex begins degrading MPF’s cyclin subunit. In this way, MPF triggers a chain of events that leads to its own destruction.

40. Cell-Cycle Checkpoints
Many other protein complexes are involved in regulating the cell cycle.
There are three distinct cell-cycle checkpoints during the four phases of the cell cycle. Interactions among regulatory molecules at each checkpoint allow a cell to “decide” whether to proceed with division. If these regulatory molecules are defective, the checkpoint may fail and cells may start dividing in an uncontrolled fashion.

41. G1 Checkpoint
The first and most important checkpoint occurs late in G1. This checkpoint determines whether the cell will continue through the cycle and divide, or exit the cycle and enter G0.
Four factors affect whether cells pass the G1 checkpoint:
Cell size
Nutrient availability
Social signals from other cells
Health of DNA

42. Will a Given Cell Pass the G1 Checkpoint?
Cells must be large enough to split into two functional daughter cells.
Food must be sufficient for cell growth.
Cells in multicellular organisms pass (or do not pass) through the G1 checkpoint in response to signaling molecules from other cells.
The p53 protein either pauses the cell cycle or initiates apoptosis – programmed cell death – if the DNA is physically damaged.
p53 is an example of a tumor suppressor; damage to the p53 gene can lead to uncontrolled cell division.

43. G2 Checkpoint
The second checkpoint is between the G2 and M phases. Cells stop growing here if chromosome replication has not proceeded properly or if DNA is damaged.

44. Metaphase Checkpoint The third and final checkpoint is during M phase.
Cell growth ceases during metaphase if the chromosomes are not properly attached to the mitotic spindle.
This mechanism prevents incorrect chromosome separation that could give daughter cells the wrong number of chromosomes.
The three cell-cycle checkpoints prevent the division of cells that are damaged or that have other problems, and they prevent the growth of mature cells that should stay in the G0 state.

46. Cancer: Out-of-Control Cell Division
Cancer is a common, sometimes lethal disease that affects many humans.
Cancer is a complex family of diseases caused by cells that grow in an uncontrolled fashion, that invade nearby tissues, and that spread to other sites in the body.
Cancers vary widely in time of onset, growth rate, seriousness, and cause.
Despite their differences, all cancers arise from cells in which cell-cycle checkpoints have failed.

48. Types of Cancerous Cell Defects
Cancerous cells have two types of defects:
Defects that make the proteins required for cell growth active when they should not be
Defects that prevent tumor suppressor genes from shutting down the cell cycle

49. Properties of Cancer Cells
A tumor forms when one or more cells in a multicellular organism begin to divide in an uncontrolled fashion.
Benign tumors are noninvasive and noncancerous.
Malignant tumors are invasive. They can spread throughout the body via the blood or lymph, and initiate secondary tumors.
When cancer cells detach from the original tumor and invade other tissues, this is called metastasis.

51. Cancer Involves Loss of Cell-Cycle Control
Cancers are thought to arise from cells with defects in the G1 checkpoint.

52. Social Control
Cells respond to signals from other cells, so that cells divide only when their growth benefits the whole organism. This is known as social control.
Social control is based on growth factors–polypeptides or small proteins released by cells that stimulate division in other cells.
Generally, cell cultures will not grow unless growth factors are present.
Cancer cells, however, divide without growth factors. They are no longer subject to social control at the G1 checkpoint.

53. Social Controls and Cell-Cycle Checkpoints
Rb protein enforces the G1 checkpoint, keeping the cell in G0.
Excessive growth factors can override the inhibitory effects of Rb.
Cyclin synthesis is triggered and cyclin-Cdk complexes are activated, leading to activation of the S-phase proteins.
In some human cancers, the G1 cyclin is overproduced, permanently activating Cdk, which then continuously phosphorylates its target proteins.
Either excessive growth factors or cyclin production in the absence of growth factors can cause cyclin overproduction.

55. Cancer Is a Family of Diseases
Many different types of defects can cause the G1 checkpoint to fail.
Most cancers result from multiple defects in cell-cycle regulation.
Most cancers develop only after several genes have been damaged.
The combined damage is enough to break cell-cycle control and induce uncontrolled growth and metastasis.
Each type of cancer is caused by a unique combination of errors.