The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)
Dec 19, 2015
The Hallmarks of Cancer
Hanahan and Weinberg, Cell 100:57-70 (2000)
Cell Regulatory Networks Important in Cancer Cells
Hanahan and Weinberg, Cell 100:57-70 (2000)
Figure 8.3b The Biology of Cancer (© Garland Science 2007)
STARTor
Restriction Point
Figure 8.1 The Biology of Cancer (© Garland Science 2007)
Figure 8.6 The Biology of Cancer (© Garland Science 2007)
The Main Jobs of the Cell Cycle:
1. To accurately transmit the genetic information!
2. To maintain normal ploidy; i.e. diploidy!
Euploidy: additions of whole chromosome setse.g. n, 2n, 3n, 4n = haploid, diploid, triploid, tetraploid
Aneuploidy: additions or subtractions of one or more single chromosomese.g. 2n + 1, 2n -1, 2n + 2, etc.
Figure 8.4 The Biology of Cancer (© Garland Science 2007)
Properties Required for Transmission of Chromosomes During Cell Division
1. One and only one centromere
2. Functional telomere at both ends
3. Chromosomes must be fully replicated
4. Chromosomes cannot be too large or too small
S Phase of the Cell Cycle
Mitosis
Mitosis in an Early Fruit Fly Embryo
Figure 8.3a The Biology of Cancer (© Garland Science 2007)
Mitosis in NewtLung Cells
blue = DNAgreen = microtubules
Metaphase in a mammalian cell
Anaphase in a plant cell
G1-S and G2-M are the major control points in the cell cycle
Rao and Johnsoncell fusion experiments
1. Fuse M phase cell with interphase cell: Interphase nucleus enters M
2. Fuse S phase cell with G1 cell: The G1 nucleus enters S phase
3. Fuse S phase cell with G2 cell: The G2 nucleus does not enter S phase
Cyclin Dependent Kinases Regulate the Cell Cycle
Experimental Systems Important for Cell Cycle Studies
Arbacia punctulata
Xenopus laevisSchizosaccharomyces pombe
Saccharomyces cerevisiae
Fission yeast: Schizosaccharomyces pombe
Budding Yeast Saccharomyces cerevisiae
Isolating Temperature Sensitive Mutants in Haploid Yeast
Permissive (low) temperature Restrictive (high) temperature
Cdc Mutants Arrest at the Same Cell Cycle Phase
Phosphorylation of CDK Targets Changes Their Activity
Now performsa cell cycle function
cdc mutant growingat permissive temp (23C)
cdc mutant growth arrested after 6 hrs at non-permissive temp (36C)
The Behavior of a Temperature Sensitive cdc Mutant
How to Clone cdc Genes in Yeast
Cdc Genes Encode Proteins Needed for DNA ReplicationStudies in S. cerevisiae
Cdc Genes Encode Proteins Needed for the G2-M Transition:Studies in S. pombe
cdc2+ encodes a kinase Moreover = cdc28 in S. cerevisiae!
Cyclin was Discovered in Sea Urchin Embryos
ProteinLevel
Time
cyclin A cyclin B
M M M
can stimulate to
lay lots of eggs
mitosis mitosis mitosis
(Spisula is actually a clam.)
Overview of the frog life cycle
1 mm
spermtadpole feeds, grows
and becomes an adult frog
OOCYTE GROWS WITHOUT DIVIDING(MONTHS) FERTILIZATION
FERTILIZED EGG DIVIDES WITHOUT GROWING(HOURS)
The Maturation of Frog Eggs
The Maturation of Frog Eggs
An Assay for Maturation Promoting Factor (MPF)
Yoshio Masui, 1971
MPF Activity Peaks Before Each Cell Division
Moreover, MPF has kinase activity
Purification of MPF: The Birthof Cyclin Dependent Kinases
This is cdc2+!!(Cdc28 in
S. cerevisiae)
This is cyclin!!
Which = cdc13+
in S. pombe
Phosphorylation of CDK Targets Changes Their Activity
Now performsa cell cycle function
The Nobel Prize in Physiology or Medicine, 2001
“for their discovery of key regulators of the cell cycle”