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BMSC 220 > The Cell Cycle & Apoptosis > Flashcards

The Cell Cycle & Apoptosis Flashcards

1
Q

What are the four coordinated processes involved in eukaryotic cell cycles?

A
  1. cell growth
  2. DNA replication
  3. distribution of the duplicated chromosomes to daughter cells
  4. cell division
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2
Q

What does mitosis (the M phase) involve?

A

Nuclear division and the separation of daughter chromosomes, usually ending with cell division.

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3
Q

What is cytokinesis?

A

The actual division of a cell following mitosis

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4
Q

What is interphase?

A

The period between mitoses when the chromosomes are decondensed and distributed throughout the nucleus

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5
Q

What happens in the G1 phase?

A

cell growth and making proteins for DNA replication

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6
Q

What happens during the S phase?

A

DNA replication and DNA synthesis

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7
Q

What happens during the G2 phase?

A

proteins for mitosis are made

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8
Q

What can reactivate cell division?

A

appropriate extracellular signals such as growth factors

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9
Q

What happens in the G0 stage?

A

cells remain metabolically active but no longer proliferate

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10
Q

What is the progression of cells through the cell cycle regulated by?

A

Extracellular signals from the environment and internal signals that monitor and coordinate the various processes that take place during different cell cycle phases.

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11
Q

What are the 2 questions that the cell is faced with before initiating mitosis and cell division?

A

Should I divide?

Am I capable of dividing properly?

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12
Q

What is the decision point in late G1 phase called in yeast cells? In animal cells?

A

“START” in yeast cells and the restriction site in animal cells

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13
Q

What are the factors determining the “START” point in yeast cells?

A

available nutrients, size, and mating factors

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14
Q

What are the factors determining the restriction site in animal cells?

A

extracellular growth factors

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15
Q

What happens when a cell passes the first decision point?

A

It is committed to proceed through S phase and the rest of the cell cycle (even if external factors such as growth factors are no longer present)

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16
Q

What are the four cell cycle checkpoints that control the “am I capable of dividing properly?” question?

A
  1. G1: ensures damaged DNA is repaired before being replicated in S phase
  2. S: continues monitoring DNA integrity
  3. G2: prevents initiation of mitosis if DNA is not completely replicated/is damaged
  4. M (spindle assembly checkpoint): inhibits spindle assembly if chromosomes aren’t distributed accurately to daughter cells
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17
Q

What happens if there is a problem at any of the 4 cell cycle checkpoints?

A

Cell cycle arrest will occur

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18
Q

What is the cell cycle of all eukaryotes controlled by?

A

A conserved set of protein kinases, which are responsible for triggering the major cell cycle transitions

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19
Q

What are cyclins?

A

proteins which regulate the activity of the enzymes which regulate the cell cycle

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20
Q

What are cyclin dependent protein kinases (Cdks)?

A

phosphorylating enzymes that are regulated by cyclins

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21
Q

What is the interaction of cyclins with Cdks responsible for?

A

triggering the major cell cycle transitions and for the progression of the cell cycle through its major checkpoints

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22
Q

What were the 3 model organisms used to identify the key molecules responsible for cell cycle regulation?

A
  1. frog oocytes
  2. yeast
  3. sea urchins
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23
Q

What was discovered through the study of frog oocytes?

A

Identified the maturation promoting factor (MPF)

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24
Q

What is the purpose of MPF?

A

MPF is a general regulator of the transition from G2 phase to M phase

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25
Q

What was discovered through the study of yeast?

A

Mutations in genes called cell division cycle mutants (cdcs) caused various cell cycle arrests, and these genes were found to encode for protein kinases.

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26
Q

What do protein kinases play a key role in?

A

In the progression of the cell cycle through its restriction point and its various checkpoints

27
Q

What was discovered during the study of sea urchins?

A

Following fertilization, sea urchin embryos go through a series of rapid cell divisions where distinct proteins are synthesized and degraded during the cell cycle (cyclins)

28
Q

What are the two key subunits of MPF?

A

Cdk1 (first identified in studies of yeast) and cyclin B (first identified in studies of sea urchins)

29
Q

What is Leland Hartwell known for?

A

The “START” site in yeast and the concept of cell cycle checkpoints

30
Q

What is Timothy Hunt known for?

A

The discovery of cyclins

31
Q

What is Paul Nurse known for?

A

Identifying cyclin dependent kinase

32
Q

What are Yoshio Masui and Dennis Smith known for?

A

The discovery of MPF

33
Q

How is Cdk1 regulated?

A

Cdk1 must first undergo a number of phosphorylation and dephosphorylation events itself before it can phosphorylate other proteins to initiate entry into the M phase

34
Q

How does Cdk1 regulate the cell cycle?

A

After Cdk1 binds to cyclin B (in G2), it is first phosphorylated in 3 positions (1 activating position and 2 inactivating positions), followed by the desphosphorylation of 2 of these positions to become an active MPF and allow the cell into the M phase.

35
Q

What are the 2 families of inhibitor proteins?

A
  1. proteins that interact with monomeric Cdk and prevent association with cyclin
  2. proteins that inhibit activity of Cdk/cyclin dimers
36
Q

What occurs during mitosis (karyokinesis)?

A
  • chromosomes condense
  • nuclear envelope breaks down
  • cytoskeleton reorganizes to form the mitotic spindle
  • chromosomes move to opposite poles
37
Q

What occurs during cell division (cytokinesis)?

A
  • golgi apparatus fragments

- cytoplasm divides

38
Q

What regulates all aspects of karyokinesis and cytokinesis?

A

the Cdk1/cyclin B complex

39
Q

What do aurora and polo-like kinases form with Cdk1?

A

a positive feedback loop

40
Q

What are aurora and polo-like kinases important for?

A

chromatin condensation and separation, and cytokinesis

41
Q

What are cohesins?

A

proteins that bind to DNA in the S phase and maintain the linkage between sister chromatids following DNA replication

42
Q

What are condensins activated by? What do they do?

A

Activated by phosphorylated Cdk1, replace the cohesins, and induce chromatin condensation

43
Q

What occurs during metaphase (spindle assembly checkpoint)?

A
  • anaphase promoting complex is inactive by the mitotic checkpoint complex (MCC) that forms at the unattached kinetochores
  • complex dissociates when all chromosomes are aligned on the mitotic spindle
44
Q

What occurs during anaphase? What does this result in?

A

Anaphase activates the APC/C which results in:

  • degradation of cyclin B by ubiquination
  • degradation of remaining cohesion proteins allowing separation of chromatids
45
Q

What is nuclear envelope breakdown driven by?

A

phosphorylation of nuclear lamins by Cdk1/cyclin B, which causes the lamins to depolymerize

46
Q

What drives golgi apparatus fragmentation?

A

The golgi apparatus fragments into small vesicles at mitosis due to phosphorylation of golgi matrix proteins by Cdk1

47
Q

How is dynamic instability of microtubules increased?

A

As the mitotic spindles are formed, microtubule associated proteins or phosphorylated by Cdk1, which results in increased dynamic instability of microtubules.

48
Q

What is cytokinesis triggered by?

A

The inactivation of Cdk1

49
Q

What is required for cyclin D synthesis to continue?

A

Cyclin D synthesis continues as long as growth factors activating the pathway continue to be present.

50
Q

What does the continues synthesis of cyclin D allow for?

A

allows for continued cell division by driving cells past their restriction point

51
Q

What is a tumour suppressor gene?

A

a gene whose inactivation leads to tumour development

52
Q

What is a key substrate of Cdk4,6/cyclin D?

A

a tumour suppressor known as retinal blastoma (Rb)

53
Q

What is retinal blastoma? What does it control?

A

Rb is a transcriptional regulatory protein that controls cell cycle progression

54
Q

What does activated Rb maintain?

A

maintains a family of transcription factors (E2F) in an inactive form in either the G1 or G0 phase

55
Q

What does phosphorylation of Rb by the cdk/cyclin D complex cause?

A

causes Rb to dissociate form the transcription factors allowing transcription of genes involved in cell cycle progression to be expressed

56
Q

What is p53?

A

A transcription factor that is stabilized and activated by phosphorylation from both ATM (protein kinase) and Chk2 (checkpoint kinase)

57
Q

What does the activation of p53 result in?

A

p53 induces the expression of a Cdk inhibitor which results in cell cycle arrest

58
Q

What are oncogenes/

A

proteins such as cyclin D and Ras which induce cell proliferation

59
Q

What is programmed cell death (apoptosis)?

A

a carefully regulated process in which damaged or non-functional cells are removed from a tissue

60
Q

What is apoptosis characterized by?

A

cleavage of chromosomal DNA, chromatin condensation, and fragmentation of both the nucleus and the cell

61
Q

Why were caenorhabditis elegans used to study apoptosis?

A
  • relatively simple organism
  • short life cycle
  • transparent (individual cells can easily be viewed during development)
  • has a determined cell lineage
62
Q

What was identified in the study of C. elegans?

A

several mutations in genes that either prevented cell death in cells normally programmed to die, or caused cell death in cells that would not normally die

63
Q

What are caspases?

A

proteases that are the “executioners of apoptosis” and initiate many of the degradative processes of apoptosis

64
Q

Why were caspases given their name?

A

They have a cystine in the active site, and the proteases cut after an aspartate residue

BMSC 220 (13 decks)

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