Basic cell cycle outline
Graph of Cyclin Concentration Over Time
Cyclin-CDK / Cell Cycle Overlay
Cyclin / CDK model including Cyclin C-CDK3 and Cyclin H-CDK7
Role of Cyclin C-CDK3
Drives re-entry from G0
Role of Cyclin H-CDK7-MAT1
Enables Cyclin B-CDK1 activity
Role of Cyclin D-CDK4/6
Activated during G1 phase of the cell cycle. The level of cyclin D-CDK activity is important in helping the cell decide whether or not to divide. The higher the level of activity, the more likely it is to divide.
Role of Cyclin E-CDK2
Role of Cyclin A-CDK2
Role of Cyclin A-CDK1
Role of Cyclin B-CDK1
Regulation of Cyclin-CDKs
Three mechanisms of CDK regulation
1. Synthesis and degradation (E3 ubiquitination) of cyclin and CDK subunits
2. Regulation by other protein kinases and phosphatases
3. Inhibitors of CDK activity (INKs)
Coordination of Growth and Cell Cycle Progression
Relevance of integrin signaling to cell division
Prokaryotic vs Eukaryotic DNA replication
Segregation of Origin Assembly and DNA Replication
Prereplication Complex Regulation
The prereplication complex is activated to begin transcription by. . .
E or A Cyclins and associated CDKs
Initiation of Replication
Binds to ssDNA during replication to prevent it from reannealing.
Regulation of S phase replication
DNA Polymerase utilized in replication
Keeps Pol δ attached to the DNA during replication
What keeps initiation factors from binding to the new strands of DNA that are being produced during replication?
Phosphorylation by high levels of Cyclin E/Cyclin A-CDK complexes
Sustained CDK activity during S phase and G2 is essential to . . .
1. Promote completion of DNA replication
2. Prevent re-initaition and re-replication of replicated DNA
Fundamental logic of the Cyclin-CDK solution to the problem of segregating replication and initiation
Mitosis imaged by fluorescence microscopy
Location of the G2-M Checkpoint
Kinase which is activated by signaling from active DNA replication forks. Phosphorylates Cyclin B-CDK1 complexes on two N-terminal residues (Thr14, Tyr 15) which inhibits Cyclin B-CDK1 activity.
This prevents mitosis from starting until DNA replication is complete.
Phosphatase which is activated when replication forks disappear (replication is over)
Removes the inhibitory Thr14 and Tyr15 phosphate groups on Cyclin B-CDK1, which were placed by Wee1, and allows the cell to enter mitosis.
How Cyclin B-CDK1 breaks down the nuclear lamina
Condensation of DNA for mitosis
This condensation is mediated by Cyclin B-CDK1
Centromeres and Kinetochores
Cohesins are cut as part of the _____ to _____ transition.
Cohesins are cut as part of the metaphase to anaphase transition.
During mitosis, the Golgi and ER. . .
. . .become fragmented into vesicles and are passively distributed to the two daughter cells.
Each sister chromatid in a single chromosome is attached to microtubules coming from one end of the mitotic spindle
Metaphase-Anaphase Checkpoint Location
Sequences Required for Cyclin B degradation
Sequence that targets the protein for regulated degradation (not necessarily constitutive)
The E3 for Cyclin B is. . .
Anaphase promoting complex / cyclosome
(Not to be confused with adenomatous polyposis coli, the tumor suppressor gene product, or antigen presenting cell)
Role of Cdc20 in Cyclin B regulation
Cdc20 is the receptor which associates with the APC/C complex in order to target Cyclin B for degradation.
Cdc20 recognizes only phosphorylated Cyclin B, and so it will not degrade Cyclin B prior to the metaphase-anaphase transition.
Inhibits separase until APC/C is activated. It senses APC/C activation because. . . it is an APC/C target!
This is how Cyclin B-CDK1 destruction is tied to the beginning of anaphase: Once APC/C is active, all of the sudden Cyclin B-CDK1 and securin are both gone.
The Separase-Securin System
_____ is what is sensed by the spindle checkpoint
Tension is what is sensed by the spindle checkpoint
If a chromosome is not under tension, it means is must not be attached properly, and thus the spindle checkpoint is activated.
Drop in CDK activity at the end of mitosis and cytokinesis leads to. . .
. . . inactivating dephosphorylation of the proteins that form pre-replication complexes.
These will be reactivated after the G1/S transition.
We can boil down the logic of the cell cycle to an oscillation between. . .
We can boil down the logic of the cell cycle to an oscillation between CDK activity and APC/C activity