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Cell Cycle Flashcards

1
Q

What is the cell cycle?

A

functional process that a cell goes through until it has divided into 2 genetically identical daughter cells

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2
Q

What are the main functions of the cell cycle?

A
  • replace lost body cells (sloughing of GI epithelia, wound healing, inflammatory response)
  • replaced old cells
    (old RBCs, destruction in spleen)
  • undergo clonal expansion (lymphocytosis in infection)
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3
Q

What are the 2 main stages of the eukaryotic cell cycle?

A
  • interphase

- mitosis (M phase)

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4
Q

What are the sub-phases of interphase?

A

G1, S, G2

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5
Q

What are the stages of mitosis?

A 
PMAT-C
prophase
(pro)metaphase
metaphase
anaphase
telophase

cytokinesis

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6
Q

Which cells CAN enter the cell cycle?

A

Cells with:

  • HIGH MITOTIC ACTIVITY
  • that divide upon appropriate stimulation
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7
Q

Which cells CANNOT enter the cell cycle?

A

post-mitotic cells = terminally differentiated

these are usually highly specialised cells, which are permanently arrested from cell cycle (senescent)

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8
Q

What are the 3 main types of cells that CAN enter the cell cycle?

A
  • labile
  • quiescent (stable)
    [ - permanent ]
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9
Q

What are labile cells?

A

rapidly divide with short G1 phase
never in G0 phase
“rapidly dividing” cells (most affected in chemo

e.g. skin, epithelia haematopoetic tissue

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10
Q

What are quiescent/stable cells?

A

Leave G0 phase when stimulated (e.g. damage)
Enter into G1 phase from G0

e.g. hepatocytes, perioseal cells, lymphocytes

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11
Q

What are permanent cells?

A

remain in G0 phase
Can only be replaced by stem cells

e.g. skeletal muscle cells (stem cells = satellite cells), neurons, RBCs

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12
Q

What is the G1 phase of interphase in cell cycle?

A
  • starting point in cell cycle
  • longest phase
  • one of the gap phases (M-> S phase)
  • stimulus required for entry from G0 phase
  • phase where cell prepares for S phase
  • move on when cell is properly prepared for S phase
  • if not, cell cycle is arrested at G1 phase
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13
Q

What is the S phase of interphase in cell cycle ?

A

DNA replication

  • occurs semi-conservatively
  • anti-sense strands used as template for new strand (sense) synthesis
  • Binding of complimentary bases via Chargaff’s rule
  • High replcation fidelity
  • will double DNA content at end of S phase
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14
Q

What mediates the high replication fidelity in S phase of cell cycle?

A
  • complimentary base pairing (GC, AT): incorrect pairing will cause unstable H-bond formation
  • proof reading DNA Pol activity
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15
Q

When does the cell progress from S phase to G2 phase?

A

when all chromosomes have been duplicated correctly (and checked for errors)

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16
Q

What is G2 phase?

A
  • shorter than G1 phase (usually)
  • preparation for mitosis
  • organelle synthesis (e.g. centrioles and mitotic spindle proteins)
  • driven by G2 regulatory proteins
  • any errors found will arrest the cells in this G2 phase
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17
Q

When do cells progress from G2 phase to M phase?

A

All in order for M-phase

correct organelles, DNA proofread and checked for errors etc

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18
Q

What is M phase?

A

= mitotic phase

- MITOSIS + CYTOKINESIS

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19
Q

What is mitosis?

A

= PMAT

- division of nucleus

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20
Q

What is cytokinesis?

A

final stage of cell cycle

physical division of cytoplasm and organelles

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21
Q

What occurs in prophase?

A
  • condensation of chromosomes
  • centrosomes move to opposite poles
  • mitotic spindle forms
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22
Q

What occurs in PROmetaphase?

A
  • disintegration of nuclear envelope

- chromosomes attach to mitotic spindle

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23
Q

What occurs in metaphase?

A
  • centrosome are at opposite poles

- chromosomes line up at the equator

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24
Q

What happens at anaphase?

A
  • pairs of chromosomes separate with one chromosome moving to each pole (soon to be new cell)
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25
What happens at telophase?
- one chromosome from each original pair reaches at each pole - chromosomes decondense - nuclear envelope reforms
26
What happens at cytokinesis?
division of cytoplasm into identical daughter cells
27
What is meiosis?
- production of 4 haploid cells - 2 processes of cell division (cytokinesis) - homologous recombination occurs - CHIASM structure allows DNA exchange between DNA inherited from mother and father
28
What is mitosis?
- production of 2 diploid cells - only one stage of cell division (cytokinesis) - no homologous recombination - therefore no DNA exchange between tightly linked chromosomes
29
What happens at the end of M-phase?
- some cells re-enter cell cycle at G1 and divide again (this continues until senescence - associated with loss of telomerase activity) - some cells become quiescent (e.g. via contact inhibition) - some cells exit G1 and enter G0 for specialisation (terminal differentiation)
30
What is the function of cell cycle checkpoints?
- correct errors detected prior to next phase - withdraw from cell cycle if major error detected - apoptosis may be stimulated if errors cannot be corrected
31
Where are the 3 major checkpoints in the cell cycle?
- G1/S checkpoint - G2/M checkpoint - M checkpoint
32
What does the M-checkpoint control?
- controls progression from metaphase to anaphase
33
Which cytokine can stop cell progression at G1/S checkpoint?
TGF-beta
34
Give an example of a trigger for arresting a cell at the M-chekpoint
- if spindles are not correctly aligned in the central axis (equator) of cell
35
What triggers are screened at the G1/S phase checkpoint?
- cell size - nutrient and growth signals sufficient? - DNA damage?
36
What triggers are screened at the G2/M phase checkpoint?
- correct DNA replication | - DNA damage
37
triggers are screened at the M phase checkpoint?
- correct separation of chromatids | - centrally aligned mitotic spindle
38
How can phosphorylation activate/inhibit a protein? What are the advantages of this modification type?
- alter physical properties, causing conformational change - alter hydrophobicity or interactions - speedy process - does not need new protein synthesis to re-activate or inhibit (temporary modification) - reversible
39
What are cyclins?
- involved in cell cycle regulation | - tightly regulated abundance during cell cycle (specific to cell-cycle phase)
40
What are the CDKs?
= cyclin dependent kinases - stable abundance throughout cell cycle - inactive until bound by cyclin - degradation/removal of bound cyclin will terminate Cdk activity
41
What is the function of the cyclin-CDK complex?
phosphorylation of other target proteins to activate them
42
How do cyclin-CDKs function in the up regulation of DNAPol by Rb?
Rb is usually sequestered in a complex with E2F (inactive) At specific stages (G1), cyclin-CDK complex phosphorylates Rb This causes Rb to dissociate from E2F. E2F then translocates to nucleus to up regulate DNAPol expression
43
What is the retinoblastoma protein?
= Rb (tumour suppressor gene) - key cyclin-CDK target protein in G1 and G1/S checkpoint - regulation of DNAPol transcription
44
What are CDKi proteins?
= inhibitors of cyclin-dependent kinases
45
What are the 2 types of CDKi proteins?
- Inhibitor of kinase 4 family (INK4) | - CDK Inhibitory Protein/Kinase Inhibitory Protein (CIP/KIP) family
46
How do INK4 proteins work?
= CDKi proteins e.g. p15 (INK4b) expression is stimulated by TGF-beta specifically
47
How do CIP/KIP proteins work?
= CDKi proteins e.g. p21 (Cip) Expression stimulated WEAKLY by TGFb. Expression STRONGLY stimulated by DNA damage (involves p53). Inhibit all other CDK-cyclin complexes (late G1, G2 and M). Are gradually sequestered by G1 CDKs thus allowing activation of later CDKs.
48
What is the p53 protein?
- activated in response to DNA damage | - Phospho-p53 is ACTIVE form (longer half life than inactive form)
49
What is the main function of p53?
induced CDKi expression (e.g. p21) causes cell cycle arrest (in G1) until repair of DNA damage
50
What happens if DNA damage cannot be repaired when the cell cycle is arrested?
cell dies by apoptosis [important function of tumour suppressors)
51
What is a mitogen?
- cytokines which stimulate cell proliferation - bind to cell-surface receptors-> promote cell cycle initiation and proliferation - some mitogens are encoded by photo-oncogenes
52
Give an example of a mitogen (implicated in breast cancer)
Her2 ER PR
53
What cell cycle mechanisms are dysfunctional in cancer cells?
- ignore normal checkpoint signals - enter S phase even with genetic damage - unresponsive to contact inhibition - unresponsive to apoptotic cells
54
What are the types of DNA damage?
- mismatched bases - chemical modification of bases - bulky DNA adducts - dsDNA breaks
55
Which drugs target the S-phase of the cell cycle?
- 5-fluoro-uracil (5-FU) | - bromodeoxyuridine (BrdU)
56
How does 5-FU work?
targets S-phase | - prevents synthesis of dTMP needed for DNA replication. Leads to apoptosis
57
How does BrdU work?
targets S-phase | - used in research to identify active replicating cells by labelling of thymidine incorporated into new DNA
58
Which drugs target the M-phase of the cell cycle?
- colchisine - vinka alkloids - paclitaxel (taxol)
59
How does colchicine work?
targets M-phase | - stabilises free tubular, arresting cell cycle and causing death
60
How do Vinka alkaloids work?
block beta tubular polymerisation and so inhibit cell division
61
How does Paclitaxel work?
targets M-phase | stabilises microtubules, preventing breakdown of polymerisation

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