Topic 14: The Cell Cycle Flashcards
1
Q
Cell Cycle
A
- cycle of growth and division within a cell
2
Q
Four coordinated processes
A
- cell growth
- DNA replication
- distribution of the duplicated chromosomes to daughter cells
- cell division
3
Q
Phases of Cell Cycle
A
- Mitosis (M Phase)
2. Interphase
4
Q
Mitosis Phase
A
- nuclear division (karyokinesis)
- most dramatic stage of cell cycle
- corresponding to the separation of daughter chromosomes
- ends with cell division
5
Q
Cytokinesis
A
- the actual division of a cell following mitosis
- division of cytosol
6
Q
Interphase
A
- period between mitoses when chromosomes are decondensed and distributed throughout the nucleus
- nucleus appears morphologically uniform
7
Q
Quiescent
A
- non-dividing stage (G0)
- neurons and many other cell types remain in this stage
- cells remain metabolically active but no longer proliferates
8
Q
G1 Phase
A
- “START” phase in yeast cells
- “restriction site” in animal cells
- after passing decision point, cell is committed to proceed through cell cycle
9
Q
Checkpoints
A
- G1
- S
- G2
- DNA damage checkpoints - M: spindle assembly checkpoint
- problem = cell arrest
10
Q
G1 Checkpoint
A
- ensures damaged DNA is repaired before being replicated in S phase
11
Q
S Checkpoint
A
- continues monitoring DNA integrity ensures DNA that is damaged is repaired
12
Q
G2 Checkpoint
A
- prevents initiation of mitosis if DNA is not completely replicated or is damaged
13
Q
M Checkpoint
A
- inhibits spindle assembly if chromosomes not distributed accurately to daughter cells
14
Q
Regulators of Cell Cycle Progression
A
- Cyclins
- Cyclin dependent protein kinases (Cdk’s)
- responsible for triggering major cell cycle transitions and for progression of the cell cycle through checkpoints
15
Q
Cyclins
A
- proteins which regulate the activity of enzymes which regulate the cell cycle
16
Q
Cdk’s
A
- phosphorylating enzymes that are regulated by cyclins
17
Q
3 Key Model Organisms
A
- frog oocyte: key reg. factor in cytoplasm
- yeast: protein kinase
- sea urchins: cyclic protein expression
18
Q
Frog Oocytes
A
- maturation triggers entry into meiotic division from G2 arrested oocytes
- identified Maturation Promoting Factor (MPF)
- -> pushed cell to be in M phase from G2 phase even when arrested
19
Q
Yeast
A
- strains carrying mutations in specific genes were identified that were defective in cell cycle progression
- encoded cell cycle regulator conserved in all eukaryotes (Cdk1)
20
Q
Sea Urchin Embryos
A
- go through a series of rapid cell divisions where distinct proteins that are synthesized and degraded during cell cycle were identified
- discovered proteins called cyclins (A and B)
21
Q
Molecular Characterization of MPF
A
- purified from frog oocytes
- made up of two subunits
1. Cdk1 (yeast)
2. Cyclin B (sea urchins) - highly conserved regulator of the cell cycle
22
Q
Cdk1 Regulation
A
- Cdk1: alone, unphosphorylated in interphase
- Cyclin B binds to Cdk1 (G2)
- Cdk1 is phosphorylated at 3 sites
i) activating site
ii and iii) inactivating site (2 sites) - 2 inactivating site are dephosphorylated allowing singly phosphorylated Cdk1/Cyclin B complex to activate other proteins that will carry the cell into mitosis
- APC/C = protein - activated Cdk1 = degradation of Cyclin B
23
Q
APC/C
A
- anaphase-promoting complex/cyclosome
24
Q
G1
A
- passage through start regulated by Cdk1 in association with G1 Cyclins
- Cyclin D
25
Q
G2
A
- entry into mitosis is regulated by Cdk1 in association with G2 cyclins
- Cyclin B
26
Q
Mechanisms of Cdk Regulation
A
- association with cyclins
- activating phosphorylation f threonine around position 160
- inhibitory phosphorylation of threonine 14 and tyrosine 15
- association with Cdk inhibitors (CKI’s)
27
Q
Cdk Inhibitors
A
- Interact with monomeric Cdk and prevent association with cyclin
- Inhibit kinase activity of Cdk/cyclin dimer
28
Q
Karyokinesis
A
- mitosis
- the chromosomes condense
- the nuclear envelope of most cells breaks down
- the cytoskeleton reorganizes to form the mitotic spindle
- chromosomes move to opposite poles
29
Q
Cytokinesis
A
- Cell division
- the Golgi apparatus fragments and the cytoplasm divides
30
Q
Targets of Cdk1/Cyclin B
A
Karyokinesis 1. chromatin condensation 2. nuclear envelope breakdown Cytokinesis 3. fragmentation of Golgi apparatus 4. spindle formation
31
Q
Cohesins
A
- proteins that bind to DNA in S phase
- maintain linkage between sister chromatids following DNA replication
32
Q
Condensins
A
- are activated by ℗’d Cdk1 and replace the cohesins (except those at the centromere)
- induce chromatin condensation
33
Q
MCC
A
- mitotic checkpoint complex
- inactivates APC/C
- forms at unattached kinetochores
- dissociates when all chromosomes are aligned on the mitotic spindle
34
Q
APC/C in Anaphase
A
1) degradation of cyclin B
2) degradation of remaining cohesion proteins allowing separation of chromatids
35
Q
Breakdown of the Nuclear Envelope
A
- driven in part by phosphorylation of nuclear lamins by Cdk1/cyclin B, which causes the lamins to depolymerize
36
Q
Fragmentation of Golgi Apparatus
A
- fragments into small vesicles at mitosis (may be absorbed into ER or distributed directly to daughter cells at cytokinesis) due to ℗’n of Golgi matrix proteins by Cdk1
37
Q
Spindle Formation
A
- microtubule associated proteins are phosphorylated by Cdk1 (and other kinases), which results in increased dynamic instability of microtubules
38
Q
Cytokinesis is triggered by..
A
inactivation of Cdk1
39
Q
Cytokinesis Process
A
A contractile ring of actin and myosin II filaments forms beneath the plasma membrane beginning in anaphase but is most active during telophase and mediates cytokinesis
40
Q
Cyclin D
A
- critical link btw growth factors signalling and cell cycle progression
41
Q
Cyclin D Synthesis
A
- continues as long as growth factors activating this pathway continue to be present
- drives cells past restriction point and allows for continued cell division
- rapidly degraded and cell division stops quickly in the absence of growth factors
42
Q
Tumor Suppressor Gene
A
- a gene whose inactivation leads to tumor development
43
Q
Rb
A
- A key substrate of cdk4,6/cyclin D
- tumor suppressor
- a transcriptional regulatory protein that controls cell cycle progression, and is encoded by the Rb tumor suppressor gene that was identified by the genetic analysis of retinoblastoma
- key role in coupling the cell cycle machinery to the expression of genes required for cell cycle progression and DNA synthesis
44
Q
Cell Regulation of Rb an dE2F
A
- Actived Rb maintains E2F (family of transcription factors) in an inactive form in either G1 or G0
- Phosphorylation of Rb causes it to dissociate from E2F, allowing E2F to activate transcription of genes involved in cell cycle progression = cell cycle passes restriction point and enters S phase
45
Q
Growth Factors
A
- presence of growth factors stimulates Cyclin D expression which phosphorylates Rb thereby allowing E2F to activate genes required for progression of cell cycle past the restriction point in G1 and to move into S phase
46
Q
Cell Proliferation
A
- regulated not only by growth factors but also by a variety of signals that act to inhibit cell cycle progression
47
Q
DNA Damage Checkpoint
A
- initiated by protein kinases (ATR and ATM)
- components of protein complexes that recognize damaged or unreplicated DNA
- These kinases phosphorylate and activate checkpoint kinases (Chk1 and Chk 2) that bring about cell cycle arrest
48
Q
p53
A
- a target of checkpoint kinases
- a transcription factor that is stabilized and activated by phosphorylation from both ATM and Chk1
- -> increase in p53 levels in response to DNA damage
- -> induces expression of Cdk inhibitor = cell arrest
- -> arrest allows from repair
49
Q
Loss of p53 Function
A
- removes block to cell cycle arrest
- allows damaged DNA to be replicated and cell cycle to complete
- is a tumor suppressor
50
Q
Regulation of Cell Death
A
- cell death must be balanced by cell renewal
- cells normally lost in tissues due to sloughing off, necrosis, or through an active process (apoptosis)
51
Q
Apoptosis
A
- Programmed Cell Death
- carefully regulated so that the fate of individual cells meets the needs of the organism as a whole
- removal of damage/nonfunctional cells
- key role in eliminating unwanted cells
52
Q
Abnormalities in Apoptotic Process
A
- cancers, autoimmune diseases, neurodegenerative disorders
- some diseases result from accumulation of errors over multiple generations of cell division
53
Q
Characteristics of Apoptotic
A
- an active, tightly regulated process of programmed cell death
- characterized by cleavage of chromosomal DNA, chromatin condensation and fragmentation of both the nucleus and cell
54
Q
C.Elegans
A
- short life cycle
- transparent
- identified several mutation in genes that prevented cell death in cells normally programmed to die, or caused cell death in cell that would not normally die
- ced-3 encodes caspase
55
Q
Caspase
A
- proteases that are “executioners of apoptosis”
- initiate many of the degradative processes of apoptosis
- exist in cell as inactive precursors and are activated by proteolytic cleavage
56
Q
p53 and Apoptosis
A
- if DNA damage is beyond repair:
- p53 levels continue to increase
- p53 induces apoptotic genes PUMA and Noxa
- initiates a cascade of reactions which activates cascade 9 resulting in apoptosis
