1
Q
Mencione the cell cycle phases.
A
• Interphase
- G1
- S
- G2
• Mitosis
• G0
2
Q
Tell me the characteristics of G1 phase.
A
Last from hours to months
Cell growth during this phase
There is one chromatide per chromosome
Synthesis of RNA
Occurs after mitosis
3
Q
What’s the G0 phase?
A
Variable duration state
The cells enter after exiting G1 phase
Those cell are differeciated
Most mature cells are in this state
4
Q
Mencione the Mitosis stages.
A
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
5
Q
Tell me the characteristics of G2 phase.
A
Last for 2 to 5 hours
Synthesis of proteins further necessary for mitosis
Repair of DNA replication errors
6
Q
Tell the characteristics of S phase.
A
Last for 8 h
DNA replication results in two chromatide per chromosome
Synthesis of protein necessary for the DNA packing (histones)
7
Q
Effects of EGF on the cell cycle.
A
• Promotion of the proliferation
- Trough its pathways it phosphorylate and mark to ubiquitilation the p27^Kipl. This inhibits Cyclin E- CDK 2 complex & Cyclin D- CDK 4/6. Necessary to the G1- S phase transition.
8
Q
Effects of PDGF on the cell cycle.
A
• Promotion of proliferation. G1 to S phase by upregulating Cyclin D and CDK 4&6
9
Q
Cyclin-dependent Kinase’s characteristics
A
- A type of inactive kinease that most be activated in order to transition from a phase to another.
- Present in all the phases.
- Activated via binding to cyclins to form cyclins/CDK complex.
- Inactivated by CDKIs (inhibitor proteins) if any error is detected.
10
Q
Types of cyclins.
A
A to E
11
Q
Tell examples of Tumor suppressors.
A
- BRCA-1/BRCA-2 (DNA repair proteins) defect = breast cancer
- NFI = neurofibromatosis type 1
- p53 = Li- Fraumeni syndrome
- APC = adenomatous polyposis
- pRb = retinoblastoma
12
Q
Tell me the basics principles of cell cycle regulation.
A
- Insulin
- EGF
- EPO
- Cyclins/CDK complex
- Platelet-derived growth factor
13
Q
Functions of the EGF.
A
- Development: especially in tissues such as skin, lungs and gastrointestinal tract.
- Wound healing: stimulating the proliferation of keratinocytes and fibroblasts.
- Maintenance of epithelial tissue.
14
Q
Clinical implications of over expression or mutation of EGF.
A
- Non-small cell lung cancer
- Colorectal cancer
- Head & neck squamous cells carcinoma
15
Q
Mencione Mitosis’ phases
A
- Prophase
- Prometaphase
- Metaphase
- Anaphase
- Telophase
16
Q
Prophase’s key points
A
- Chromosome condensation, mark the beginning of this phase.
- Centrosome separation
- Formation of the mitotic spindle
- Formation of more organelles (mitochondria).
- Degradation of the nucleus into small vesicles mark the end of this phase.
17
Q
What’s the centrosome?
A
It’s a chromosomal region into wich proteins like kinetochore, the point of origin of the mitotic spindle. Form by two centrioles surrounded for a matrix from wich the microtubules emerge.
18
Q
Prometaphase’s key points.
A
- The mitotic spindle is fully formed.
- The microtubules of the mitotic spindle attach to the kinetochore, emanating from opposite sides. When the chromosomes are aligned on the metaphase plate the metaphase phase has been reached.
19
Q
Metaphase’s key points.
A
- Maximal condensation of chromatin.
- The chromosome must be aligned on the equator of the cell. (Mitotic spindle checkpoint).
- When the link between sister chromatids breaks. Mark the end of this phase.
20
Q
Spindle checkpoint’s key points.
A
- Mediated by a complex of proteins called the MCC (mitotic checkpoint complex)
- Those proteins inhibits the APC/C until every chromosome is aligned.
21
Q
Dynein’s function.
A
- It’s a motor protein.
- Aid the attach to various microtubules of the mitotic spindle to chromosomes.
22
Q
Anaphase’s key points.
A
- Cell elongation.
- Begging of the cytokinesis.
- Separation of sister chromatids, due to the dissolution of the centromere by the enzyme separase. Marks the transition to anaphase.
23
Q
Telophase’s key points.
A
- Disintegration of the mitotic spindle.
- Formation of a new nuclear membrane.
- Decondensation of the chromosome.
- Synthesis of Ribosomal RNA (rRNA).
- Cytokinesis is almost complete by the end of this phase.
24
Q
Cyclin A key points.
A
- Transcription begin at G1 and peak in the middle of S phase.
- It’s complex with CDK 2 allow the transition from G1 to S.
- It’s complex with CDK 1 allow the transition from S to G2.
25
Function of Cyclin B.
- Regulate G2 checkpoint.
26
Function of Cyclin C.
- Allow transition from G0 to G1, bind with CDK 3.
- Regulate **gen transcription** by **phosphorylated transcription factors** and **RNA polymerase II**.
27
Functions of CyclinD.
- Transition from G1 to S bind with CDK 4,6.
- Initiation of protein replication by inactivation of **pRb**.
28
Cyclin E functions.
- Allow the transit from G1 to S binding/activating CDK 2.
- Initiation of the DNA synthesis along with CDK 2.
29
G1 checkpoint key point.
- Control of Nuclear/Cytoplasmic ratio.
- Enough nutrients levels.
- DNA damage.
- Regulated by:
• Cyclin D/CDK4.
• p53 tumor suppressors.
• Proapoptotic active proteins of the BCI-2 family, such as Bax and Bak.
30
Function of p53 tumor suppressor in the regulation of G1 checkpoint.
- If *DNA damage is reparable*, it activate the **p21** causing the arrest of the cell cycle by the inactivation of the **G1/S & S-CDK** complexes through the *inactivation of the pRb*.
- Also through the activation of the **p27**, this inactivate directly the **Cyclins/CDK complexes**.
- If *DNA damage is irreversible* produce apoptosis trough active proteins of the **family of BCI-2**, such as **Bax & Bak**.
31
G2 checkpoint highlights.
- Check for DNA damage.
- DNA replication if there is any errors.
- Initiate mitosis by phosphorylation of various proteins.
32
Regulation of G2 checkpoint.
- By Mitosis Promoting Factor **(MPF)**, composed by **CDK1/cyclin B**.
33
M checkpoint key points.
- Happen between metaphase and anaphase.
- Ensure correct alignment of the chromosomes and sister chromatids at the equatorial plane before the separation of sister chromatids.
34
Mencione the cell types according to it replication properties.
- Labile cells.
- Permanent cells.
- Quiscent (Stable cells)
35
Labile cells characteristics.
- Rapidly dividing cells
- Short G1
- Lack of G0
- Fast cell turnover makes these cell specifically vulnerable to chemotherapy.
36
Labile cells examples.
- Epithelial cells.
- Germ cells.
- Hematopoietic cells.
37
Quiescent cells characteristics.
- May enter G1 phase from G0 when stimulated.
38
Quiescent cell’s examples.
- Cells in endocrine and exocrine glands.
- Hepatocytes.
- Lymphocytes.
- Periosteal cells.
- Cells of the proximal covoluted tubule.
39
Permanent cells key points.
- Remain in G0 phase.
- Regenerate via cell differentiation from steam cell.
40
Permanent cells examples.
- Skeletal & cardiac muscle cells.
- Red blood cells.
- Neurons.
41
p53 tumor suppressor key points.
- Encode by the TP53 gem.
- Activated in response of:
• cell stress
• DNA damage
• oxidative stress
• oncogene activation
• hypoxia.
- Negative regulation: MDM2 by promoting its ubiquitilation and proteosomal degradation.
42
Aurora Kinase’s functions.
- Centrosome maturation.
- Interactions of chromosomes with microtubules.
- Activation of the contractile ring of actin myosin II filaments, necessary to cytokinesis.
43
Cohesins key points.
- Member of the structural maintenance of chromatin **(SMC)**.
- Bind to DNA on S phase, maintaining the linkage between sister chromatids following DNA replication.
- Breakdown of the Golgi apparatus into vesicles.
- It’s replace for condensins as the cell enter M phase, in most of the chromosomes but the centromere.
44
Condensins key points.
- Member of the family of the Structural Maintenance of Chromatin (SMC).
- Induce chromatin condensation into DNA loops, leading to the formation of metaphase chromosomes.
45
- Function of the CDK1/cyclin B complex on the breakdown of the nuclear lamina.
- **Phosporilation of the lamins** result in depolymerization of nuclear lamina into laminate dimers.
- **Phosporylates several proteins** in the inner nuclear membrane and the nuclear pore complex.
- **Breakdown the Golgi apparatus** into vesicles, absorbed by the ER or distributed to the daughter’s cells.
- **Activation of the APC/C ubiquitin ligase**, produce the *degradation* of the **securin**, activating the **separase**, producing the final *degradation of the cohesins*.
46
Aurora Kinase Family. Types, location and function.
**Aurora A kinase.**
- Location:
• Centromeres and spindle poles.
- Functions:
• Centromere maturation.
• Mitotic spindle assembly.
• Regulate Mitotic Spindle checkpoint.
• Promote Mitotic Entry through the phosphorylation of several substrates, such as some necessary to the Mitotic spindle formation.
**Aurora B kinase.**
- Location:
• Chromosomes.
- Functions:
• Chromosomes condensation on early stages of mitosis.
• Proper attachment of mitotic spindle microtubules to the kinetochore.
• Regulation of the M checkpoint.
• Regulation of the Cytokinesis.
USMLE Step 1
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