Transcript Cell Cycle 1

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)
START
or
Restriction Point
Figure 8.3b The Biology of Cancer (© Garland Science 2007)
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 sets
e.g. n, 2n, 3n, 4n = haploid, diploid, triploid, tetraploid
Aneuploidy: additions or subtractions of one or more single chromosomes
e.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
Mitosis in Newt
Lung Cells
blue = DNA
green = microtubules
Figure 8.3a The Biology of Cancer (© Garland Science 2007)
Metaphase in a mammalian cell
Anaphase in
a plant cell
G1-S and G2-M are the major
control points in the cell cycle
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
Rao and Johnson
cell fusion experiments
Cyclin Dependent Kinases Regulate the Cell Cycle
Experimental Systems Important for Cell Cycle Studies
Saccharomyces cerevisiae
Schizosaccharomyces pombe
Arbacia punctulata
Xenopus laevis
Fission yeast: Schizosaccharomyces pombe
Budding Yeast Saccharomyces cerevisiae
Isolating Temperature Sensitive
Mutants in Haploid Yeast
Cdc Mutants Arrest at the Same Cell Cycle Phase
Permissive (low) temperature
Restrictive (high) temperature
Phosphorylation of CDK Targets Changes Their Activity
Now performs
a cell cycle function
The Behavior of a Temperature Sensitive cdc Mutant
cdc mutant growing
at permissive temp (23C)
cdc mutant growth arrested after
6 hrs at non-permissive temp (36C)
How to Clone cdc Genes in Yeast
Cdc Genes Encode Proteins Needed for DNA Replication
Studies 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
can stimulate to
lay lots of eggs
Protein
Level
cyclin A
cyclin B
Time
M
M
M
mitosis
mitosis
mitosis
(Spisula is actually a clam.)
Overview of the frog life cycle
OOCYTE GROWS WITHOUT DIVIDING
(MONTHS)
FERTILIZATION
FERTILIZED EGG DIVIDES WITHOUT GROWING
(HOURS)
1 mm
sperm
tadpole feeds, grows
and becomes an adult frog
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 Birth
of 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 performs
a cell cycle function
The Nobel Prize in Physiology or Medicine, 2001
“for their discovery of key regulators of the cell cycle”