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Cell Cycle
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17
Medical
Professional
09/10/2010

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Term
Cell Cycle Checkpoints
Definition
1)G1 DNA-damage checkpoint=DNA has to be in good shape before cell can enter the cell cycle.
2)Restriction Checkpoint-Make sure everything is suitable before DNA replication (last part of G1)
3)S-phase DNA checkpoint-Middle of S phase, is it going or completed?
4)Unreplicated DNA damage checkpoint(end of S)
5)G2 DNA-damage checkpoint (repetitive)
6)Spindle-assembly checkpoint
7)Chromosome seperation checkpoint separate
Term
Cell Cycle Checkpoints Overview
Definition
1)Arrest the cell cycle when genomic integrity is threatened.
2)Regulate cell cycle progression based on environmental signals (growth factors, extra-cellular matrix attachment, cell-cell contacts).
3)Checkpoints include an intra-S phase checkpoint, a spindle-assembly checkpoint, a spindle-position checkpoint and a DNA damage checkpoint.
4)Because of these critical functions, mutations in key checkpoint genes contribute to a variety of human diseases.
Term
Mitotic Cdk complexes
Definition
1)MPF (mitosis-promoting factor)
Regulates mitosis by activating:
a)Chromosome condensation
b)Nuclear membrane breakdown
c)Mitotic apparatus assembly
d)Chromosome alignment
2)Activates ANAPHASE-promoting complex (APC)***
3)Cyclins are then degraded by APC (Cyclins have to be degraded before cells can divide; phosphorylation dependent regulation of ubiquitation. Cdh1, cyclin that binds to APC is deactivation through phosphorylation and vice versa. can be induced by EXTERNAL or INTERNAL signaling)
Term
Different phases in cell cycle
Definition
1) Mitotic-prophase, metaphase, anaphase.
2) Action steps of the cell cycle - S or the synthesis phase (where DNA incorporation occurs)
3) G1-restriction point or "start" phase are the the events leading to a decision--is the cell big enough? is the environment favorable?
Term
G2 checkpoint
Definition
Critical step prior to mitosis where cell asks 1)Has all the DNA been replicated? Are there any errors? Is there DNA damage?
Term
Metaphase checkpoint
Definition
Exit from mitosis
Can the cell undergo cytokinesis?
Term
Catastrophic Event
Definition
Failure to interpret a checkpoint correct will result in progression before completion.
Mitotic catastrophe.
Chromosome breaks, misalignments, mis-segration.
Term
Cell Cycle Clock
Definition
1)You have
a)Growth Activators
b)Growth Inhibitors
2)Key players
a)Integrins
b)Nutrient status
3)Cell can go into
a)G0-quiescent (become terminally differentiated)
b)enter into active cell cycle
Term
D1
Definition
Cyclin that together with Cyclin-Dependent Kinases control progression through the Cell Cycle
Term
Pairings of cyclins with cyclin-dependent kinases
Definition
Multiple forms in mammalian cells
Cyclins D, E, A, B
CDK(CDC2)
Also, multiple cyclins can bind to the same cyclin kinase.
Term
Cyclins and CDKs
Definition
--CDKs:
1)do not exhibit kinase activity unless associated with a cyclin
2)9 Mammalian CDKs (not all cell are cycle genes)
--Cyclins:
1)concentration increase & decrease in phase with cell cycle
2)necessary for CDK activity and aid in substrate specificity
3)20 mammalian Cyclins
4)Classes of Cyclins:
a)G1 Cyclins – Help push a cell past the restriction point
b)G1/S Cyclins – act at the end of G1/ commit a cell to DNA replication
c)S-Cyclins – act in S to initiate DNA replication
d)M-Cyclins – promote the events of mitosis
Term
General principles by which progression through the cell cycle is regulated
Definition
1)Activation of CDKs is driven by the sequential expression and association with cyclin subunits
2)The destruction of cyclins ensures a unidirectional cell cycle (presence of destruction box allows cyclin to be tagged by ubiquitin)
3)The inhibition of assembled CDK-cyclin complexes, either by phosphorylation or by the binding of inhibitory proteins (negative regulators) delays CDK activation and slows cell cycle progression in adverse conditions.
Term
Mitosis is controlled by _____
Definition
Matriculation Promotion Factor (MPF)
Low levels of cyclin & MPF activity during interphase (G1, S, G2) and high levels of cyclin & MPF activity during mitosis.
MPF artificially implanted in non-dividing cells undergo mitosis!
Term
Cohesin Complexes
Definition
Machinery that connects sister chromatids.
Needs to be altered to allow seperation.
A Smc1Beta and Smc3 stalk on each of two subunits connected by Scc1.
Term
Mechanism of action of APC
Definition
Activates separase (though ubiquitination of securin), leading to cleavage of Kleisin (Scc1)
Term
Down Syndrome
Definition
Likelihood of child born with Down Syndrome (Trisomy at chromosome 21) increases with maternal age.
This is because as mother gets older, 1 component of the cohesin component is lost or weakened (Smc1Beta) resulting in mis-separation during anaphase.
Term
Retinoblastoma
Definition
1)An cell cycle inhibitor
2)D2 (regulates start)
3)Retinoblastoma protein, Rb, is a critical substrate of cyclin D-CDK4/6 (complexed by D1 and D2) and Cyclin E-CDK2
4)Rb gets phosphorylated (goes from hypo-D-CDK4/6 to hyper (E-CDK2) through R point)
5)Rb is usually complexed with E2F (transcriptional activator) and phosphorylation of Rb leads to release of E2F.
6)Mutation in RB gene results in constitutive entry into the cell cycle.
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