1. The Cell Cycle
Chapter 12

2. A. Overview
Continuity of life based upon reproduction of cells, or cell division
Both unicellular and multicellular organisms reproduce using cell division, but reasons differ

3. Unicellular Multicellular Reproduction Development Growth Repair
(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).

4. Cell Cycle G0 phase G1 phase S phase G2 phase Mitosis INTERPHASE
Cell division (mitosis in red) is integral part of cell cycle
Cell Cycle
G0 phase
G1 phase
S phase
G2 phase
Mitosis
INTERPHASE

5. B. DNA Organization
Cell division results in genetically identical daughter cells
Cells duplicate genetic material (DNA replication) before they divide, ensuring each daughter cell receives exact copy of DNA
cell’s inherited genetic information is called its genome

6. DNA molecules in a cell packaged into chromosomes
Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division
50 µm

7. In eukaryotes, two types of cells:
Somatic (body) cells have two sets of chromosomes
Gametes (sex cells) have one set of chromosomes

8. Chromosomes are packages of DNA wrapped with help of proteins called histones
Composed of two identical sister chromatids attached at centromere

9. Chromosome levels organization (smallest to biggest):
dsDNA
Nucleosome
Coiled solenoid/nucleosome
Chromatin
Supercoiled (condensed) chromatin
Chromosome

12. Why are histones “sticky?” Five different interactions with DNA!
Histones are positive, DNA phosphate groups are negative
DNA backbone and amide group on histone form H bonds
Nonpolar interactions between sugars on histone and DNA
Salt bridges and H bonds between basic amino acids on histone and phosphate oxygens on DNA
groove insertions histone tails fit into grooves on DNA molecule

13. C. Cell Division
In preparation for cell division, DNA is replicated and chromosomes condense

14. Each duplicated chromosome has two sister chromatids, which separate during cell division
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.

15. Eukaryotic cell division consists of
Mitosis, the division of the nucleus
Cytokinesis, the division of the cytoplasm
In meiosis, sex cells are produced after a reduction in chromosome number

16. cell cycle consists of mitotic phase Interphase INTERPHASEG1
S (DNA synthesis) G2
Cytokinesis Mitosis
MITOTIC (M) PHASE

17. Interphase can be divided into subphases:
G1 phase: cellular contents excluding chromosomes are duplicated
S phase: DNA synthesis; each of 46 chromosomes is duplicated by cell
G2 phase: cell double-checks duplicated chromosomes for errors, makes any needed repairs
G0 phase: cell cycle arrested (halted)

19. Differs between plants and animals
The mitotic phase is made up of mitosis and cytokinesis. Mitosis consists of five distinct phases (PPMAT)
Prophase (early prophase)
Prometaphase (late prophase)
Metaphase
Anaphase
Telophase (and Cytokinesis)
Differs between plants and animals

20. 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

21. 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

24. arises from centrosomes, includes spindle microtubules and asters
mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis
arises from centrosomes, includes spindle microtubules and asters
Some spindle microtubules attach to kinetochores of chromosomes and move chromosomes to metaphase (midline) plate

25. Kinetochores microtubules
Centrosome
Chromosomes
Microtubules
0.5 µm
1 µm
metaphase plate

26. Prophase Nuclear membrane breaks down
Spindle fibers emerge from centrioles
PROPHASE
Early mitotic spindle
Aster
Centromere
Chromosome, consisting of two sister chromatids

27. Prometaphase Centrioles move to opposite poles
Spindle fibers attach to centromeres
PROMETAPHASE
Fragments of nuclear envelope
Non-kinetochore microtubules
Kinetochore
Kinetochore microtubule

28. Metaphase Chromosomes Migrate to Midline METAPHASE Metaphase plate
Centrosome at one spindle pole
METAPHASE
Spindle
Metaphase plate

29. Anaphase Spindle fibers contract, pulling sister chromatids apart
Chromatids move along kinetochore microtubules to opposite poles
Anaphase
Daughter chromosomes
ANAPHASE

30. EXPERIMENT
The microtubules of a cell in early anaphase were labeled with a fluorescent dye that glows in the microscope (yellow).
Spindle pole
Kinetochore

31. Telophase & Cytokinesis
Non-kinetechore microtubules from opposite poles overlap and push against each other, elongating cell
Genetically identical daughter nuclei form at opposite ends of the cell

32. In plant cells, during cytokinesis a cell plate forms
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

33. In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow
Contractile ring of microfilaments
Daughter cells
100 µm
(a) Cleavage of an animal cell (SEM)

34. Mitosis in a plant cell Chromatin condensing Nucleus Chromosome1
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
Chromatin condensing

35. D. Binary Fission
Prokaryotes (bacteria) reproduce by a type of cell division called binary fission
bacterial chromosome replicates
two daughter chromosomes actively move apart

36. Replication continues. One copy of origin is now at each end of cell.
Chromosome replication begins. Soon thereafter, one copy of origin moves rapidly toward other end of cell.
Replication continues. One copy of origin is now at each end of cell.
Replication finishes. Plasma membrane grows inward, and new cell wall is deposited.
Two daughter cells result.
Origin of
replication
E. coli cell
Bacterial
Chromosome
Cell wall
Plasma
Membrane
Two copies
of origin
Origin

37. E. Evolution of Cell Cycle
Since prokaryotes preceded eukaryotes by billions of years, 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

38. A hypothetical sequence for evolution of mitosis:
Prokaryotes. During binary fission, origins of daughter chromosomes move to opposite ends of cell. Proteins may anchor daughter chromosomes to specific sites on plasma membrane.
Bacterial chromosome

39. Dinoflagellates. In these unicellular protists, nuclear envelope remains intact during cell division, chromosomes attach to nuclear envelope. Microtubules pass through nucleus inside cytoplasmic tunnels, reinforcing spatial orientation of nucleus, which then divides in fission process reminiscent of bacterial division.
Chromosomes
Microtubules
Intact nuclear envelope

40. Diatoms. In this group of unicellular protists, nuclear envelope also remains intact during cell division. But microtubules form a spindle within nucleus. Microtubules separate chromosomes, and nucleus splits into two daughter nuclei.
Kinetochore
microtubules
Intact nuclear
envelope

41. Most eukaryotes. In most eukaryotes, including plants and animals, spindle forms outside nucleus, and nuclear envelope breaks down during mitosis. Microtubules separate chromosomes, and nuclear envelope then re-forms.
Centrosome
Kinetochore
microtubules
Fragments of
nuclear envelope

42. F. Regulation of Cell Cycle
cell cycle regulated by molecular control system
frequency of cell division varies with type of cell
cell cycle differences result from regulation at molecular level

43. Cytoplasmic signals: molecules present in cytoplasm regulate progress through cell cycle
EXPERIMENTS
In each experiment, cultured mammalian cells at two different phases of cell cycle were induced to fuse.
RESULTS

44. Experiment 1 S G1 M G1
Experiment 2
RESULTS S S M M
When a cell in S phase was fused with cell in G1, G1 cell immediately entered S phase—DNA was synthesized.
When a cell in M phase was fused with cell in G1, G1 cell immediately began mitosis— a spindle formed and chromatin condensed, even though chromosome had not yet been duplicated.

45. CONCLUSION
Results of fusing cells at two different phases of cell cycle suggest that molecules present in cytoplasm of cells in S or M phase control progression of phases.

46. sequential events of 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

47. clock has specific checkpoints where cell cycle stops until a go-ahead signal is received
G1 checkpoint G1 G0
(a) If a cell receives a go-ahead signal at the G1 checkpoint, cell continues on in cell cycle.
(b) If cell does not receive a go-ahead signal at G1checkpoint, cell exits cell cycle and goes into G0, a non-dividing state.

48. Two types of regulatory proteins are involved in cell cycle control:
Cyclins and cyclin-dependent kinases (Cdks)

49. activity of cyclins and Cdks fluctuates during cell cycle
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

50. Both internal and external signals control the cell cycle checkpoints
Growth factors stimulate other cells to divide

51. A sample of connective tissue was cut up into small pieces.
Scalpels
EXPERIMENT
A sample of connective tissue was cut up into small pieces.
Enzymes were used to digest the extracellular matrix, resulting in a suspension of free fibroblast cells.
Cells were transferred to sterile culture vessels containing a basic growth medium consisting of glucose, amino acids, salts, and antibiotics (as a precaution against bacterial growth). PDGF (growth factor)was added to half the vessels. The culture vessels were incubated at 37°C. 3 2 1
Petri plate
Without PDGF
With PDGF

52. 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
Cells anchor to dish surface and
divide (anchorage dependence).
When cells have formed a complete single layer, they stop dividing (density-dependent inhibition).
If some cells are scraped away, remaining cells divide to fill gap and then stop (density-dependent inhibition).
Normal mammalian cells. The availability of nutrients, growth factors, and a substratum for attachment limits cell density to a single layer.
(a)
25 µm

53. Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence
25 µm
Cancer cells do not exhibit anchorage dependence or density-dependent inhibition.
Cancer cells. Cancer cells usually continue to divide well beyond a single layer, forming a clump of overlapping cells.
(b)

54. Cancer cells
Do not respond normally to body’s control mechanisms
Form tumors
After the AP test, we will read “The Immortal Life of Henrietta Lacks” which discusses growing cancer cells in a petri dish

55. Malignant tumors invade surrounding tissues and can metastasize
Exporting cancer cells to other parts of the body where they may form secondary tumors
Tumor
Glandular
tissue
Cancer cell
Blood vessel
Lymph vessel
Metastatic Tumor
A tumor grows from a single cancer cell. 1
Cancer cells invade neighboring tissue. 2
Cancer cells spread through lymph and blood vessels to other parts of the body. 3
A small percentage of cancer cells may survive and establish a new tumor in another part of the body. 4

56. metastasis