Lecture #13 – 10/3 – Dr. Wormington
The Molecular "Logic" of the Cell Cycle – Recap
1. Cdks generally present throughout cell cycle
but are inactive w/o cyclin subunits.
2. Cyclin subunits synthesized in
discrete cell cycle phases
G1 phase Cyclins D & E
G2 phase Cyclins A & B
3. Cdks phosphorylate
relevant target proteins to alter
their activities at discrete times.
Note that Cdk activity rises
gradually as phase progresses.
4. Cyclins are degraded at end of
each cell cycle phase.
Hence name "cyclin" as levels
"cycle". Degradation necessary to
proceed to next phase of cell cycle.
5. Enables unidirectional progression
through cell cycle.
WHY HAVE MULTIPLE CYCLINS & CDKS?
Initiation of
Chromosome
Condensation
& Mitosis
Different Cdk-Cyclin Complexes
Phosphorylate Unique Subsets of
Protein targets
e.g., nuclear vs cytoplasmic
Growth
Factors
Commitment to
Cell Division
Stimulation of
DNA Replication
Initiation of
DNA Replication
Making it fit – Human DNA must be compacted >100,000X
Packaging achieved by progressive assembly of "naked" DNA
Into increasingly compact DNA-protein complexes = Chromatin
Nucleosome = Fundamental Unit
Core = 2X ea. H2A, H2B, H3, H4
+ Charged Histones Neutralize
- Charged DNA for "1st order"
Compaction
HI Linker
Outside
Core
Physiological [K+] Provides Additional
Charge Neutralization to Further Compact
Nucleosomes
Compaction in Interphase Cell
Metaphase Chromosome
Electron Micrographs of Chromatin
10 nm "Beads on String"
30 nm Condensed Structure
"Head-On" View"
H2A
H2B
H3
H4
"Side" View
Structure of
The Nucleosome
Derived by
X-ray
crystallography
Mitosis: An Exquisitely Choreographed Process
Comprised of Distinct Events
The BIG Picture
• Condense the Chromosomes
• Generate Mitotic Spindle
• Breakdown Nuclear Envelope
• Attach Chromosomes to Spindle
• Segregate Chromosomes to Daughter Cells
• Cytokinesis
• Decondense Chromosomes
• Depolymerize Spindle Microtubules
• Reform Nuclear Envelope
THE ENTIRE PROCESS IS "DRIVEN" BY THE ACTIVATION &
INACTIVATION OF THE
G2-M CDKS
Centrosome &
DNA Replication
Cell is now Tetraploid
4n
4n
2n
2n
The Centrosome aka the Microtubule Organizing Center
Source of all microtubules within the cell
Fluorescent Micrograph of
Interphase Mammalian Cells
Electron Micrograph of
A Centrosome containg its pair of
Centrioles (Microtubules (MT) radiating
Away from Centrosome are in yellow)
Centrosome Migration
Nuclear Envelope Breakdown
Sister Chromatids Condense Kinetochore Microtubules
& Joined at Centromeres
"Capture" Chromosomes
1 each/chromatid
Sister Chromatids
+ Centromere
aka Spindle Pole
Homologous
Chromosomes
DO NOT Pair in Mitosis
Chromosomes
Decondense
Nuclear Envelope
Reforms
Cytokinesis
Checkpoint
Sister Chromatids
Aligned towards Opposite Poles
Sister Chromatids
Separate
Fluorescence Micrographs of Mitotic Human Cells
DNA Microtubules
The Advantages of Sex – Meiosis Promotes Genetic Diversity
Haplontic Life Cycle
Adults & Gametes (n)
Zygote (2n)
e.g., fungi
Alternation of generations
Both (n) and (2n) adult
Stages
e.g., most plants
Diplontic Life Cycle
Adult (2n)
Gametes (n)
e.g., all animals &
some plants
The Holy Grail of Meiosis
Reduce Chromosome # from 2n to n
Ensure Each Haploid Product Has Complete Set of Chromosomes
Promote Genetic Diversity by
Recombination Between Homologous Chromosomes
Centrosome
& DNA Replication
Same as in Mitosis
Cell is Tetraploid 4n
Homologous
Chromosomes
Align Along Lengths
Synapsis
Recombination
Between Homologous
Chromosomes Occurs
4n
2n
2n
Recombination Between Homologous Chromosomes
Increases Genetic Diversity
Sister
Chromatids
Sister
Chromatids
Tetrad or
Bivalent
e.g.
Red = maternal
Chromosome 16
Blue = paternal
Chromosome 16.
Note: There can be multiple
Chiasmatas between a
pair of homologous
Chromosomes!
Parental
Nonrecombinant
Chromatids
chiasmata
Fluorescent
Micrographs of
Synapsed
Homologous
Chromosomes
In Meiotic
Prophase I in
Xenopus
Oocytes
Note: Sister
Chromatids
Are So Closely
Aligned They
Cannot Be
Distinguished
From Each
Other