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Medicine Year 1 - Semester 2 - Part 2 > Cell Division > Flashcards

Cell Division Flashcards

1
Q

State some essential features of cell division

A

Faithfully replicate genetic material

Accurately segregate into daughter cells

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2
Q

How long does it take to replicate the human genome ?

A

8 hours

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3
Q

How long does it take to segregate the replicated human genome ?

A

2 hours

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4
Q

State the phases of the cell cycle

A

INTERPHASE
G1 phase
S phase
G2 phase

M phase + Cytokinesis

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5
Q

What does S phase involve ?

A

DNA replication

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6
Q

What does the M phase involve ?

A

Mitosis - nuclear divison
Cytokinesis - cytoplasmic division

(Segregation of replicated information)

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7
Q

What happens in the G1 phase ?

A

Cell senses the environment and decides whether the cell is ready to divide.

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8
Q

What happens in the G2 phase ?

A

Cell is checking that DNA is replicated accurately.

Progression to mitosis.

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9
Q

How is cell division controlled ?

A

Critically controlled by cyclin dependent kinases.

CDK is activated when coupled to cyclin.

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10
Q

Key feature of cyclin dependent kinases (CDKs)

A

Their activity is cyclical.

There are bursts of CDK activity, coinciding when mitosis is.

CDK activity is related to the concentration of cyclin.

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11
Q

How are CDKs regulated ?

A

Cyclin dependent kinases are regulated by phosphorylation/ de-phosphorylation reactions.

This allows the cell to control precisely when the CDK is active.

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12
Q

Describe the steps leading to activation of CDK

A

CDK binds to cyclin
Inactive cyclin-CDK complex

Protein kinases, phosphorylate CDK by adding phosphates to the CDK.

This keeps it in an inactive form.

Then a phosphatase comes along and removes one of the inhibitory phosphates.

Active cyclin-CDK complex

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13
Q

What is the normal function of wee1 ?

A

Prevents cell division

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14
Q

What happens in the absence of wee1 ?

A

If you remove this inhibitory pathway, cells divide at a smaller size, than they normally would.

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15
Q

What is the normal function of Cdc25 ?

A

Promotes cell division

Cdc25 is an activating phosphatase that removes the inhibitory phosphate.

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16
Q

What happens in the absence of Cdc25 ?

A

Cells divide at a larger size than normal.

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17
Q

Function of cyclin:CDK complexes

A

Distinct cyclin:CDK complexes control events in cell division

Each CDK has a distinct cyclin.

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18
Q

State some distinct Cyclin

A

S phase cyclin: becomes active at the transition between G1 and S phase

M phase cyclin: becomes more active at entry to mitosis

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19
Q

Which cyclin is associated with the M phase ?

A

Cyclin B

(CDC2 = CDK1)

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20
Q

Which cyclin is associated with the G1 phase ?

A

Nuclear D1
(cyclin D)

(CDK4/6)

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21
Q

Which cyclin is associated with the G1-S phase ?

A

Cyclin E

(CDK2)

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22
Q

Which cyclin is associated with the S phase ?

A

Cyclin A

(CDK2) - start
(CDK1) - end

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23
Q

What happens when CDK is finished doing its job ?

A

The cyclin part becomes ubiquitinated.

Ubiquitin gets conjugated onto the cyclin, and acts as a signal, indicating completion.

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24
Q

State the steps leading to inactivation of CDK

A
  1. Active cyclin-CDK complex
  2. Ubiquitylation of cyclin
  3. Destruction of cyclin
  4. Inactive CDK
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25
Q

E1

A

Ubiquitin activating enzyme

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26
Q

E2

A

Ubiquitin conjugating enzyme

27
Q

E3

A

Ubiquitin ligase

28
Q

Describe ubiquitination

A

Ubiquitin becomes covalently bound to E1 (uses ATP)

Ubiquitin becomes transferred onto an E2 type enzyme

Last step determined by E3 (ubiquitin ligase)

E3 moves the ubiquitin from the E2 enzyme directly onto the substrate.

This happens multiple times to build up a chain of ubiquitin.

Chain of ubiquitin gets gobbled up by the proteasome.

29
Q

Key feature of ubiquitination

A

Uses ATP, so is an energy consuming process.

30
Q

What gives the ubiquitination pathway specificity ?

A

There are hundreds of E3 ubiquitin ligases.

31
Q

What is a proteasome ?

A

A complex, containing lots of different protein subunits.

  • Regulatory particle
  • Core particle
32
Q

Describe the structure of a proteasome

A

RP region - regulatory particle
CP region - core particle

33
Q

Describe the use of the RP and CP regions

A

When RP recognises ubiquitin, it opens.

This allows the peptide to move into the CP, and the peptide becomes unfolded and chopped up into component amino acids.

34
Q

State the checkpoints in the cell cycle

A

Checkpoints occur at:

  • G1
  • G2
  • M
35
Q

G1 checkpoint

A

Checks cell growth

36
Q

G2 checkpoint

A

Checks that DNA is successfully replicated

Assesses any damage to DNA

37
Q

M phase checkpoint

A

Controls progression from Metaphase to Anaphase

38
Q

When are CDK inhibitors transcribed and generated ?

A

Transcription of inhibitors can be induced if conditions are not right for cell division.

Control of the cell cycle.
Inactivate the cyclin-CDK complex

39
Q

G1/S transition

A

R-point
Regulatory point

Growth / Quiescence

40
Q

Describe a non-proliferating cell

A

Inactive protein kinase
- active CDK inhibitor

  • active Rb protein sitting on top of DNA, preventing expression of S phase genes
41
Q

Function of Rb gene

A

Rb acts as a tumour suppressor by inhibiting the transcription of S-phase genes, that code for proteins needed for DNA replication.

42
Q

Describe a proliferating cell

A

CDK inhibitor is removed

Cyclin-CDK complex is activated, which phosphorylates the Rb protein.

The phosphorylated version of Rb is inactive

Falls of the DNA, leaving the transcription factor exposed.

This enables triggering of expression of genes required for entering S phase.

43
Q

How is the Rb protein inactivated ?

A

Phosphorylation by the cyclin-CDK complex.

44
Q

Early control of the cell cycle

A

Phosphorylation and inhibiting Rb protein.

Allows progression onto S phase

45
Q

State another key target of the CDK subunits

A

CdC6 protein

46
Q

Function of the CdC6 protein

A

Plays a key role in making sure DNA is only replicated once per cycle.

47
Q

What does the response to DNA damage depend on ?

A

The stage of the cell cycle

48
Q

Describe the response to DNA damage

A

DNA damage triggers activation of:

  • p53, which directs transcription of CDK inhibitors
  • CHK2 which inhibits CdC25
49
Q

How is DNA condensation managed ?

A

A series of proteins called condensins, stack on top of each other to condense DNA into a compact stage.

50
Q

Centrosome

A

Microtubule organising centre

51
Q

What happens in pro-metaphase ?

A

Breaking down the nuclear envelope, triggered by CDKs

  • phosphorylation of the nuclear pore proteins and lamins by CDK
52
Q

Give a brief overview of mitosis

A

DNA condensation
Formation of the spindle
Nuclear envelope breakdown
Chromosomes attach
Metaphase
Anaphase

53
Q

What occurs at metaphase ?

A

Mitosis cannot proceed until chromosomes are properly attached and under tension.

Spindle checkpoint

54
Q

Anaphase

A

Spindle fibres separate the sister chromatids.

Cleaved and dissociated cohesins

Chromatids -> Chromosomes

55
Q

Function of the cohesion complex

A

Holds the sister chromatids together

Cohesion rings remain in place until anaphase, where they fall apart.

56
Q

Defects in cohesion

A

Roberts Syndrome
Very rare

Nature Genetics
37: 468-70

57
Q

Importance of cohesion proteins

A

At metaphase holds sister chromatids together.

Defects in cohesion can cause disease.

58
Q

Describe the change from metaphase to anaphase

A

Enzyme called separase cuts up the cohesin molecules.

59
Q

How is separase activity controlled ?

A

Separase is held in an inactive form by an inhibitory protein called securin.

At the right stage when the checkpoint is completed, anaphase promoting complex (APC) is activated.

60
Q

Function of active APC

A

Ubiquitylation and degradation of securin

61
Q

What do defects at the spindle checkpoint cause ?

A

Aneuploidy

  • Cell which has the wrong number of chromosomes
62
Q

How can tumor cells be targeted ?

A

Anti-mitotic drugs

63
Q

What is essential for mitotic exit ?

A

Degradation of cyclins and securin

64
Q

Cytokinesis

A

Division of the cytoplasm

2 daughter cells formed

Medicine Year 1 - Semester 2 - Part 2 (53 decks)

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