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Proteins in
the Cytoplasm
Affect Cell Cycle
Control
Cyclins
G1 cyclin (cyclin D)
S-phase cyclins (cyclins E and A)
mitotic cyclins (cyclins B and A)
Cyclin-dependent kinases (Cdks)
G1 Cdk (Cdk4)
S-phase Cdk ((Cdk2)
M-phase Cdk (Cdk1
Cyclins cycle!!!
The M Phase Promoting Factor
• Function and Composition
– Composed of Cdk 1 and cyclins A or B
– Rises when E cyclin is destroyed
during G2
– Assembly of mitotic spindle
– Breakdown of nuclear envelope
– Condensation of the chromosomes
– Phosphorylates histones, nuclear
filaments and microtubule associated
proteins that form the spindle
– Promotes the degredation of G2 cyclin
(Interesting)
– Homework:
– Investigate the function and composition of the
G1 cyclin (cyclin D) and Cdk (Cdk4) as well as
the S-phase promoting factor (cyclin E and A
and Cdk 2).
Other proteins control the cycle as
well----APC (cyclosome)
• Allows sister chromatids to separate by
triggering destruction of cohesins
• Destroys cyclin B by ubiquinating it
• Turns on G1 cyclin for the next cycle
• Degrades geminin, a protein which
prevents DNA replication
Cell cycle game
• http://nobelprize.org/educational_games/m
edicine/2001/cellcycle.html
• http://www.bama.ua.edu/~hsmithso/class/
bsc_495/spindle/spindle_web.html
Other proteins monitor the cell cycle for lethal mistakes
G0
Checkpoints
G1
checkpoints
1. DNA damage checkpoints
a. G1 checkpoint-Damage inhibits cdk2 until DNA is
repaired or cell enters apoptosis
b. G2 checkpoint -Check for completion of DNA
synthesis by monitoring Okasaki fragments.
2. Spindle checkpoints
a. check all kinetochores for attachment to spindles.
Checkpoints require proteins.
Guardians of the Genome
• p53-senses DNA damage and halt progression of the
cell cycle. It is a tumor supressor gene. Mutations in p53
are recessive. Over 50% of all cancers have mutant p53.
• ATM (ataxia telangiectasia mutated)-detects
double stranded breaks in DNA. Maintains telomere
length.
• MAD (mitotic arrest deficient)- binds a kinetochore
until a spindle connects. If no spindle attaches, entry
into anaphase is blocked by inhibiting APC. Mutations in
MAD produce aneuploidy.
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