1. The Cell Cycle and Cellular Reproduction Chapter 9

2. Outline DNA and Chromosomes Cell Division in Prokaryotes
Cell Division in Eukaryotes
The Cell Cycle
Interphase
Mitosis
Cytokinesis
Cell Cycle Control
Apoptosis
The Cell Cycle and Cancer
Characteristics of Cancer
Causes of Cancer

3. DNA and Chromosomes DNA serves as information storage molecules.
DNA is made up of nucleotides
Each nucleotide has a sugar, a phosphate group and a nitrogenous (nitrogen-containing) base
The bases are of two main types
Purines – Large bases
Adenine (A) and Guanine (G)
Pyrimidines – Small bases
Cytosine (C) and Thymine (T)

4. The four nucleotide subunits that make up DNA.
Nitrogenous base
5-C sugar

5. The two possible basepairs
DNA Double Helix
The two possible basepairs

6. Chromosomes Chromosomes are composed of DNA (40%) and protein (~ 60%).
Chromatin-tangled mass of threadlike DNA and protein in nondividing cell (seen primarily during interphase).
Chromosomes-condensed rod-shaped DNA and protein molecules during cell division.

7. Chromosomes
A typical human chromosome contains about 140 million nucleotides in its DNA.
In the cell, the DNA is coiled.
The DNA helix is wrapped around positively-charged proteins, called histones.
Eukaryotic chromosomes are linear.
Prokaryotic chromosomes are circular.

8. Cell Cycle
Set of events that occur between one cell division and the next.
In prokaryotes and unicellular eukaryotes, cell division is a form of asexual reproduction.
In multicellular eukaryotes, cell division is important for growth, development, and repair.
Plants retain the ability to divide throughout their life span
In mammals, cell division is necessary:
Fertilized egg becomes an embryo
Embryo becomes a fetus
Allows a cut to heal or a broken bone to mend

9. Function of Mitosis Permits growth and repair.
In plants it retains the ability to divide throughout the life of the plant
In mammals, mitosis is necessary:
Fertilized egg becomes an embryo
Embryo becomes a fetus
Allows a cut to heal or a broken bone to mend 9

10. Functions of Cell Division

11. Prokaryotes Have a Simple Cell Cycle
The DNA of prokaryotes is a single circular chromosome.
Cell division in prokaryotes takes place in two stages.
The DNA is replicated.
The cell elongates, then splits into two identical daughter cells.
The process is called binary fission (asexual reproduction).

12. Binary Fission of Prokaryotes

13. Cell division in eukaryotes is more complex than in prokaryotes because
1. Eukaryotic DNA is packaged differently.
It is in linear chromosomes compacted with proteins.
2. Eukaryotes contain far more DNA.

14. Levels of Eukaryotic Chromosome Organization

15. Chromosome Number in Eukaryotes
The number of chromosomes varies from species to species.
Diploids have two chromosomes of each type.
Humans have 23 different types of chromosomes
Each type is represented twice in each body (somatic) cell- diploid.
Only sperm and eggs have one of each type- haploid.
The n number for humans is n=23
Two representatives of each type
Makes a total of 2n=46 in each nucleus of a body cell.
One set of 23 from individual’s father (paternal).
Other set of 23 from individual’s mother (maternal).

16. Chromosome Numbers of Some Eukaryotes

17. Chromosomes Humans have 46 chromosomes.
The 23 pairs of chromosomes can be organized by size.
This display is termed a karyotype.

18. Eukaryotic Cell Cycle The major stages of the eukaryotic cell cycle:
Interphase
Mitosis
Cytokinesis
Interphase and mitosis each have several substages.

19. The Cell Cycle

20. Interphase Longest phase of the cell cycle.
Normal cell functions occur as well as preparation for cell division.
G1 phase:
Cell doubles its organelles
Accumulates materials needed for DNA synthesis
S phase:
DNA replication (synthesis)
Chromosomes enter with 1 chromatid each
Chromosomes leave with 2 identical chromatids each
G2 phase:
Between DNA replication and onset of mitosis (or meiosis)
Cell synthesizes proteins necessary for division
Such as microtubules for the mitotic spindle

21. Mitosis (M) Stage
Also called karyokinesis
Nuclear division
Occurs in somatic (non-reproductive) cells in animals
Occurs in meristematic tissues in plants
Daughter chromosomes divided between two daughter nuclei
Four Phases (PMAT)
Prophase
Metaphase
Anaphase
Telophase

22. Cytokinesis (C) Stage Cytoplasmic division
Results in two genetically identical diploid daughter cells.
In animal, structure that forms to separate two cells is called a cleavage furrow.
In plant cells, structure that forms to separate two cells is called a cell plate.

23. At end of S phase of interphase:
Each chromosome is duplicated.
Consists of two identical DNA double helix chains
Called sister chromatids
Attached together at a single point called a centromere
During mitosis:
Centromeres holding sister chromatids together split
Sister chromatids separate
Each becomes a daughter chromosome
Sisters of each type distributed to opposite daughter nuclei

24. Duplicated Chromosome

25. Mitosis in Animal Cells
Outside nucleus is the centrosome
The centrosome was replicated in S-phase.
Now two centrosomes
This is the microtubule organizing center.
Organizes the mitotic spindle
Each composed of a bundle of microtubules
In animals, contains two barrel-shaped centrioles.
Oriented at right angles to each other within centrosome

26. Prophase Nuclear envelope breaks down Nucleolus disappears
Chromatin condenses
Chromosomes distinguishable with microscope
Visible double (two sister chromatids attached at centromere)
Spindle apparatus forms
Two centrosomes move away from each other
Form microtubules in star-like arrays called asters

27. Prometaphase Centromere of each chromosome develops two kinetochores
On opposite sides of the centromeres
One over each sister chromatid
Spindle fibers attach at the kinetochores
Physically hook sister chromatids up with spindle apparatus.
Connect sister chromatids to opposite poles of mother cell.

28. Metaphase Chromosomes align along the equatorial plane of cell
Metaphase plate
Represents plane through which mother cell will be divided
Chromosomes are pulled around by kinetochore fibers

29. Anaphase Centromere splits Sister chromatids separate
Now called daughter chromosomes
Pulled to opposite poles by shortening of the microtubules attached to them
Cytokinesis begins in anaphase.

30. Telophase Spindle apparatus disappears
Now two clusters of daughter chromosomes
Still two of each type with all types represented
Nuclear envelopes form around the two separate cluster of daughter chromosomes
Chromosomes uncoil and become chromatin again
Nucleolus reappears in each daughter nucleus

31. Mitosis in Animal Cells

32. Overview of Mitosis
Nuclear division in which chromosome number stays constant.
DNA replication produces duplicated chromosomes.
Each duplicated chromosome is composed of 2 sister chromatids held together by a centromere.
Sister chromatids are genetically identical.
During mitosis, the centromere divides and each chromatid becomes a daughter chromosome.

33. Mitotic Phases Summarized
Prophase-nuclear membrane disappears, centrosomes migrate, spindle fibers appear
Prometaphase- the kinetochore of each chromatid is attached to a spindle fiber.
Metaphase-chromosomes line up at equator, associated with spindle fibers
Anaphase-centromeres divide, sister chromatids migrate to opposite poles, cytokinesis begins
Telophase-nuclear membranes form, spindle disappears, cytokinesis occurs

34. Cytokinesis: Animal Cells
Division of cytoplasm
Divides mother cell’s cytoplasm equally to daughter nuclei
Encloses each in it’s own plasma membrane
Often begins in anaphase
Animal cytokinesis:
A cleavage furrow appears between daughter nuclei
Formed by a contractile ring of actin filaments
Eventually pinches mother cell in two

35. Cytokinesis in Animal Cells

36. Cytokinesis: Plant Cells
Rigid cell walls outside plasma membrane do not permit furrowing
Forms a cell plate
Many small membrane-bounded vesicles
Eventually fuse into one thin vesicle extending across the mother cell
The membranes of the cell plate become the plasma membrane between the daughter cells

37. Cytokinesis in Plant Cells

38. Special Characteristics of Mitosis in Plants
Same phases as animal cells
Plant cells do not have centrioles or asters
Cytokinesis via cell plate

39. Mitosis in Plant Cells

40. Cell cycle controlled by internal and external signals
Growth factors
Received at the plasma membrane
Cause completion of cell cycle
Internal signals
Family of proteins called cyclins
Must be present for stages to progress.
Increase and decrease as cell cycle continues
Without them cycle stops at G1, M or G2
Allows time for any damage to be repaired

41. The Cell Cycle
Some cells do not go through the cell cycle. These cells are in the G0 stage-extended rest period; cell are still metabolically active; for example, some muscle cells and neurons.

42. G1 checkpoint
Cell growth is assessed at G1 checkpoint
Protein p53 stops cycle if DNA damaged
G2 checkpoint
DNA replication is assessed at G2 checkpoint
Stops cycle if DNA is not done replicating or is damaged
M checkpoint
Spindle assembly checkpoint
Stops if chromosomes not aligned properly

43. Cell Increase and Decrease
Increase and decrease of cell numbers
Cell division increases number of somatic cells
Mitosis-division of nucleus of cell
Cytokinesis-division of cytoplasm
Occurs throughout life; important for growth, development, and repair in multicellular organisms
Apoptosis- programmed cell death decreases cell number
Occurs throughout life also
Prevents abnormal cells from proliferating
Signal protein P53
Stops cycle at G1 when DNA damaged
Initiates DNA attempt at repair
If successful, cycle continues to mitosis
If not, apoptosis is initiated

44. Apoptosis Progressive series of events resulting in cell destruction.
Cells rounds up, and lose contact with surrounding cells.
Nucleus breaks up and DNA undergoes fragmentation.
Mediated by enzymes called caspases.

45. Apoptosis

46. Fingers and toes form from these paddlelike hands and feet
During fetal development, many cells are programmed to die
Programmed cell death
Human cells appear to be programmed to undergo only so many cell divisions
About 50 in cell cultures
Only cancer cells can divide endlessly

47. The Cell Cycle and Cancer
Cancer is unrestrained cell growth and division
The result is a cluster of cells termed a tumor.
Benign tumors
Encapsulated and noninvasive
Malignant tumors
Not encapsulated and invasive
Can undergo metastasis
Leave the tumor and spread throughout the body
Invade other tissues and form new tumors

48. Progression of Cancer
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
New mutations arise, and one cell (brown) has the ability to start a tumor.
primary tumor
lymphatic
vessel
blood
vessel
Cancer in situ. The tumor is at its place of origin. One cell (purple)
mutates further.
lymphatic
vessel
blood
vessel
Cancer cells now have the ability to invade lymphatic and blood vessels
and travel throughout the body.
New metastatic tumors are found some distance from the primary tumor. 48

49. Characteristics of Cancer Cells
Lack differentiation
Have abnormal nuclei
Form tumors
Mitosis controlled by contact with neighboring cells – contact inhibition
Cancer cells have lost contact inhibition
Undergo metastasis
Original tumor easily fragments
New tumors appear in other organs
Undergo angiogenesis
Formation of new blood vessels

50. Carcinogenesis – development of cancer

51. Causes of Cancer
Most cancers result from mutations in growth-regulating genes.
There are two general classes of these genes.
1. Proto-oncogenes
Encode proteins that stimulate cell division
If mutated, they become oncogenes.
2. Tumor-suppressor genes
Encode proteins that inhibit cell division
Retinoblastoma (Rb) protein acts during G1 checkpoint to inhibit cell division
p53 protein

52. Tumor-suppressor Genes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Proto-oncogenes
Growth factor receptor:
more per cell in many
breast cancers.
Ras
protein
Src
kinase
Cytoplasm
Ras protein:
activated by mutations
in 20–30% of all cancers. Rb
protein
p53
protein
Tumor-suppressor Genes
Cell cycle
checkpoints
Rb protein:
mutation in 40% of all cancers.
p53 protein:
mutated in 50% of all cancers.
Mammalian cell

53. Growth Factor Receptor Her2 and Cancer
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
(a) In a normal cell there are few Her2 membrane receptors so cell division is controlled.
Growth factor
Her2 membrane receptor
Growth Factor Receptor Her2 and Cancer
Her2 gene on DNA
(b) Some cancer cells have excess Her2 receptors. These cells divide at an increased
rate when growth factors are present.

54. Herceptin: Breast Cancer Treatment

55. Retinoblastoma Protein

56. p53 and Control of the Cell Cycle
The p53 gene plays a key role in the G1 checkpoint of cell division
p53 is also called the guardian angel gene of the cell
The p53 protein (the gene’s product), monitors the integrity of DNA
If DNA is damaged, the protein halts cell division and stimulates repair enzymes.
If the p53 gene is mutated
Cancerous cells repeatedly divide even if the DNA is damaged.
No stopping at the G1 checkpoint.

58. Telomerase Chromosomes have caps on their ends called telomeres.
Every time the cell divides part of the cap breaks off.
Eventually the cap becomes so small that the chromosome cannot be copied; limits the life span of the cell (~50 cell divisions).
Telomerase is the enzyme that can repair the ends of chromosomes.
In normal cells telomerase is inhibited so the cell will eventually stop dividing.
In cancer cells telomerase is not inhibited, so the telomeres don’t shorten; no limit on the life span of the cell.

59. Causes of Cancer Chemicals Radiation Viruses
Mutations in specific genes on chromosomes; for example a mutant p53 gene
Chromosomal mutations- extra chromosomes or missing parts of chromosomes
Telomerase