1. Cell Division Why do cells divide?
Reproduction Growth Repair & Replace

2. What is a genome?
Eukaryotic Cell
Linear
many
Circular
single

3. How much DNA in a human cell?
2 meters
# Genes?
Fewer than 20,000 code for
over 100,000 proteins

4. Chromatin DNA and proteins Protein function? Structure of DNA
Control activity of genes

5. Heterochromatin vs. Euchromatin

6. Levels of DNA coiling and folding
Nucleosome
(10 nm in diameter)
DNA double helix (2 nm in diameter) H1
Histone tail
Histones
Figure 16.21a Chromatin packing in a eukaryotic chromosome
DNA, the double helix
Histones
Nucleosomes, or “beads on a string” (10-nm fiber)

7. Fig. 16-21b 30-nm fiber Looped domains (300-nm fiber)
Chromatid
(700 nm)
30-nm fiber
Loops
Scaffold
300-nm fiber
Figure 16.21b Chromatin packing in a eukaryotic chromosome
Replicated chromosome (1,400 nm)
30-nm fiber
Looped domains (300-nm fiber)
Metaphase chromosome

8. How many chromosomes in a cell?
Somatic Cell 46
Sex Cell (Gamete) 23
Examples:
Examples:

9. Parts of a Chromosome Cohesin proteins (not cohesion!) Chromatid=
Most closely attached
Cohesin proteins
(not cohesion!)
Chromatid=
Replicated chromosome

10. Mitosis vs. cytokinesis
nuclear division
Cytoplasmic division

11. Comparing Mitosis & Meiosis
Genetically identical
Meiosis
Genetic Variation
Reduction Division 2n 2n 2n 2n n n n n n n

12. all subphases cell grows Produces proteins and all organelles
Cell Cycle
2 phases:
Interphase & mitotic phase
all subphases cell grows Produces proteins and all organelles
BOTH mitosis and cytokinesis
24 hrs
hours
5 - 6 hours
4- 6 hours
1 hour

13. Stages of Mitosis (Interphase) MITOSIS Prophase Metaphase Anaphase
Telophase & Cytokinesis
(I Probably Mixed All This up)

14. MTOC/Centrosome centrioles Aster Centrosome Microtubules Kineto-
chores
Centrosome

15. Interphase 90% of Cell Cycle G1, S, & G2 Nucleolus visible
Chromosomes replicating
Nuclear membrane intact
Single Centrosome replicates in animal cells

16. When chromosomes replicate

17. Prophase Chromatin shortens and condenses
Chromosomes appear as sister chromatids (X)
Nucleolus disappears
Nuclear membrane disappears
Centrosomes (Centrioles) move to the poles
Spindle fibers form

18. Metaphase Chromosomes meet @ equator/middle Centrioles are @ poles
Spindle fibers attach to Kinetochores
Longest phase

19. Anaphase Spindle fibers shorten and pull chromosome by centromere
Chromosomes move apart/away
Sister chromatids separate
Shortest phase
2 sets of chromosomes!!

20. Telophase & Cytokinesis
Chromosomes poles
Chromosomes lengthen & Nuclear envelope reforms
Nucleoli reappear
Cleavage furrow / Cell plate forms

21. What Phase is This?

23. Phases

24. Mitosis movie
3D tutorial
cells alive
mcgraw-hill.com

25. How Do Spindles Shorten?

26. Spindle fibers shortening

28. Cytokinesis
Animal Cell
Cleavage Furrow
Plant Cell
Cell Plate

30. G2 -> prometaphase

31. Metaphase -> cytokinesis

32. Animal Cell Division

33. Bacterial Cell Division
Binary Fission

35. Frequency of cell division
Frequency of cell division varies by cell type
embryo
cell cycle < 20 minute
skin cells
divide frequently throughout life
12-24 hours cycle
liver cells
retain ability to divide, but keep it in reserve
divide once every year or two
mature nerve cells & muscle cells
do not divide at all after maturity
permanently in G0 G2 S G1 M
metaphase
prophase
anaphase
telophase
interphase (G1, S, G2 phases)
mitosis (M)
cytokinesis (C) C

36. Regulation of the Cell Cycle
G1, G2, M checkpoints
M checkpoint
Chromosomes attached to spindles?
Can sister chromatids separate correctly?
G2 checkpoint
DNA synthesis correct?
Commitment to mitosis
G1 checkpoint/
“Restriction point”
Go / No Go
can DNA synthesis begin?
What cells never divide? G0

37. G0 phase G0 phase non-dividing, differentiated state
most human cells in G0 phase
liver cells
in G0, but can be “called back” to cell cycle by external cues
nerve & muscle cells
highly specialized
arrested in G0 & can never divide

38. Activation of cell division
How do cells know when to divide?
cell communication signals
chemical signals in cytoplasm give cue (internal signals)
Internal signals: promoting factors
External signals: growth factors
signals usually mean proteins
activators
inhibitors

39. When combined are now MPF complexes- mitosis promoting factor
Regulatory molecules
Protein kinases (Cdks- Cyclin dependant kinases)
Activate or inactivate other proteins
By phosphorylation
G1 and G2 checkpoints
Many are at a constant concentration
But are in inactive form
Cyclins
Attach to kinases to activate them
inactivated Cdk
activated Cdk
When combined are now MPF complexes- mitosis promoting factor

40. Cdks (Cyclin dependant kinases) and Cyclins ARE PROTEINS!
Regulatory molecules
Cdks (Cyclin dependant kinases) and Cyclins ARE PROTEINS!
MPF complex

41. Cyclins & Cdks
1970s-80s | 2001
Interaction of Cdk’s & different cyclins triggers the stages of the cell cycle
Cyclin is synthesized in S phase and continues to increase during G2, falls during M
Cyclin and Cdk form MPF complexes,
MPF “mitosis promoting factor” activated at end of G2
MPF phosphorylates variety of proteins, initiates mitosis
There are multiple cyclins, each with a specific role. Cyclins are unstable. Some are triggered for destruction by phosphorylation. Others are inherently unstable and are synthesized discontinuously during the cell cycle.
Oscillations in the activities of cyclin-dependent kinases (CDKs) dictate orderly progression through the cell division cycle. In the simplest case of yeast, a progressive rise in the activity of a single cyclin-CDK complex can initiate DNA synthesis and then mitosis, and the subsequent fall in CDK activity resets the system for the next cell cycle.
In most organisms, however, the cell cycle machinery relies on multiple cyclin-CDKs, whose individual but coordinated activities are each thought to be responsible for just a subset of cell cycle events.

42. Cyclins & Cdks
1970s-80s | 2001
Interaction of Cdk’s & different cyclins triggers the stages of the cell cycle
Peaks during metaphase
MPF cyclin component degrades during anaphase due to APC (anaphase promoting complex)
Cdk is inactive
There are multiple cyclins, each with a specific role. Cyclins are unstable. Some are triggered for destruction by phosphorylation. Others are inherently unstable and are synthesized discontinuously during the cell cycle.
Oscillations in the activities of cyclin-dependent kinases (CDKs) dictate orderly progression through the cell division cycle. In the simplest case of yeast, a progressive rise in the activity of a single cyclin-CDK complex can initiate DNA synthesis and then mitosis, and the subsequent fall in CDK activity resets the system for the next cell cycle.
In most organisms, however, the cell cycle machinery relies on multiple cyclin-CDKs, whose individual but coordinated activities are each thought to be responsible for just a subset of cell cycle events.
bozeman 6:30

43. G2/ Cdk / cyclin synthesized
M (Spindle) checkpoint
G2 checkpoint
Chromosomes attached at metaphase plate
Replication completed
DNA integrity
Inactive
Active
Active
G2/ Cdk / cyclin synthesized
(MPF)
Inactive M
APC
cytokinesis C G2
mitosis G1 S
Cdk inactive / G1 cyclin degraded
Inactive
MPF = Mitosis Promoting Factor
APC = Anaphase Promoting Complex
Active
G1 checkpoint
Growth factors
Nutritional state of cell
Size of cell

44. Cyclin & Cyclin-dependent kinases
CDKs & cyclin drive cell from one phase to next in cell cycle
proper regulation of cell cycle is so key to life that the genes for these regulatory proteins have been highly conserved through evolution
the genes are basically the same in yeast, insects, plants & animals (including humans)
CDK and cyclin together form an enzyme that activates other proteins by chemical modification (phosphorylation). The amount of CDK molecules is constant during the cell cycle, but their activities vary because of the regulatory function of the cyclins. CDK can be compared with an engine and cyclin with a gear box controlling whether the engine will run in the idling state or drive the cell forward in the cell cycle.

45. External signals Growth factors (50 + different kinds)
coordination between cells
Is a protein signal released by body cells that stimulate other cells to divide
density-dependent inhibition
crowded cells stop dividing
when cell binds a surface protein to another cell sends growth inhibiting signal to both cells
anchorage dependence
to divide cells must be attached to a substrate (extracellular matrix of a tissue
“touch sensor” receptors

46. Growth factor signals growth factor cell division cell surface
nuclear pore
nuclear membrane P P
cell division
cell surface
receptor
Cdk
protein kinase
cascade P
E2F P
chromosome Rb P
E2F
cytoplasm Rb
nucleus

47. Example of a Growth Factor
Platelet Derived Growth Factor (PDGF)
made by platelets in blood clots
Bind to receptors on fibroblasts(type of connective tissue)
binding of PDGF to cell receptors stimulates cell division in connective tissue
heal wounds
Erythropoietin (EPO): A hormone produced by the kidney that promotes the formation of red blood cells in the bone marrow. EPO is a glycoprotein (a protein with a sugar attached to it).
The kidney cells that make EPO are specialized and are sensitive to low oxygen levels in the blood. These cells release EPO when the oxygen level is low in the kidney. EPO then stimulates the bone marrow to produce more red cells and thereby increase the oxygen-carrying capacity of the blood.
EPO is the prime regulator of red blood cell production. Its major functions are to promote the differentiation and development of red blood cells and to initiate the production of hemoglobin, the molecule within red cells that transports oxygen.
EPO has been much misused as a performance-enhancing drug (“blood doping”) in endurance athletes including some cyclists (in the Tour de France), long-distance runners, speed skaters, and Nordic (cross-country) skiers. When misused in such situations, EPO is thought to be especially dangerous (perhaps because dehydration can further increase the viscosity of the blood, increasing the risk for heart attacks and strokes. EPO has been banned by the Tour de France, the Olympics, and other sports organizations.

48. Example of a Growth Factor
Erythropoietin (EPO): A hormone produced by the kidney that promotes the formation of red blood cells in the bone marrow. EPO is a glycoprotein (a protein with a sugar attached to it).
The kidney cells that make EPO are specialized and are sensitive to low oxygen levels in the blood. These cells release EPO when the oxygen level is low in the kidney. EPO then stimulates the bone marrow to produce more red cells and thereby increase the oxygen-carrying capacity of the blood.
EPO is the prime regulator of red blood cell production. Its major functions are to promote the differentiation and development of red blood cells and to initiate the production of hemoglobin, the molecule within red cells that transports oxygen.
EPO has been much misused as a performance-enhancing drug (“blood doping”) in endurance athletes including some cyclists (in the Tour de France), long-distance runners, speed skaters, and Nordic (cross-country) skiers. When misused in such situations, EPO is thought to be especially dangerous (perhaps because dehydration can further increase the viscosity of the blood, increasing the risk for heart attacks and strokes. EPO has been banned by the Tour de France, the Olympics, and other sports organizations.

49. Growth Factors and Cancer
Growth factors can create cancers
proto-oncogenes (ch 18)
normally activates cell division
growth factor genes
become oncogenes (cancer-causing) when mutated

50. Cancer & Cell Growth
Cancer is essentially a failure of cell division control
unrestrained, uncontrolled cell growth
What control is lost?
lose checkpoint stops

51. Immortal Cells

52. Tumors Mass of abnormal cells Benign tumor Malignant tumor
abnormal cells remain at original site as a lump
p53 has halted cell divisions
most do not cause serious problems & can be removed by surgery
Malignant tumor
cells leave original site
lose attachment to nearby cells
carried by blood & lymph system to other tissues
start more tumors = metastasis
impair functions of organs throughout body

53. Traditional treatments for cancers
Treatments target rapidly dividing cells
high-energy radiation
kills rapidly dividing cells
chemotherapy
stop DNA replication
stop mitosis & cytokinesis
stop blood vessel growth
Taxol- freeze spindles microtubules

54. freeze spindles microtubules
Taxol
freeze spindles microtubules