2: Cell replication Flashcards

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1
Q

Rate of division in embryonic cells

A

fast (compared to adult cells)

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2
Q

Rate of division in low complexity cells

A

fast (compared to high complexity)

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3
Q

Rate of division in high turnover cells

A

fast
e.g intestinal epithelial

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4
Q

Rate of division in terminally differentiated cells
e.g neurones

A

dont divide

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5
Q

Rate of division in tumour cells

A

fast

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6
Q

Cell cycle

A

G1
S
G2
(interphase)
Mitotic phase

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7
Q

Stages of interphase

A

G0- cell cycle machinery dismantled, not dormant, but non dividing
G1- decision point
S- synthesis of DNA/protein (organelles)
G2- decision point

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8
Q

M-phase

A

nuclear division
cell division (cytokinesis)

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9
Q

2 outcomes of impaired cell cycle

A

cell cycle arrest
programmed cell death

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10
Q

Cell cycle arrest

A

at check points (G1 and spindle checkpoint)
can be temporary (e.g following DNA repair)

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11
Q

Programmed cell death occurs when

A

DNA damage too great that cannot be repaired
Chromosomal abnormalities
Toxic agents

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12
Q

How do cells enter the G1 phase

A

Signalling cascade :
response to extracellular factors
Growth factors stimulate entry from G0 into G1
signal amplification
signal integration/ modulation by other pathways

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13
Q

Process of entering into G1 phase

A

GF signalling pathways induces expression of c-Myc
c-Myc promotes G0 to G1 transition

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14
Q

c-Myc is

A

c-Myc is an oncogene - overexpressed in many tumours
c-Myc - transcription factor -stimulates expression of cell cycle genes

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15
Q

What gives timing and direction to cell cycle

A

CDK activity

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16
Q

what cyclin-dependent kinases are involved in the cell cycle

A

Cdk1, Cdk2, Cdk4, Cdk6

17
Q

Where are CDKs present

A

in proliferating cells throughout cell cycle

18
Q

CDK activity is regulated by

A
  • interaction with cyclins
    -phosphorylation
19
Q

What cyclins are involved in the cell cycle

A

Cyclin A,B,D,E

20
Q

When are cyclins involved in the cell cycle

A

Transiently expressed at specific points in cell cycle

21
Q

Lifespan of cyclins

A

Regulated at level of expression
Synthesised, then degraded

22
Q

Conversion of cells from G0 to G1 by CDKs

A

1.c-Myc upregulates expression of cyclin D
Binds to inactive Cdk 4/6 complex
2. Different protein kinases add both inhibitory and activating phosphate to complex
3. Phosphatase removes the inhibitory phosphate, Cdk 4/6 Cyclin D complex becomes active, induced positive feedback loop by activating more phosphatases

23
Q

Retinoblastoma Protein

A

A molecular ‘break’
prevents tumour formation
Rb may be implicated in cancer if inactive or missing

24
Q

How Retinoblastoma Protein works

A

Rb inhibits E2F
CDK/cyclin complexes phosphorylate Rb - ‘sets E2F free’ - continuous process each CDK complex phosphorylates Rb

E2F = transcription factor and expresses genes necessary for DNA replication to continue

25
Q

Which CDK/cyclin complex is involved in allowing S phase to happen

A

CDK2-cyclin E

26
Q

Which CDK/cyclin complex is involved in allowing G2 phase to happen

A

CDK 2- Cyclin A

27
Q

Which CDK/cyclin complex is involved in allowing M phase to happen

A

CDK 1 - cyclin B

28
Q

Function of p53

A

Arrest cells with damaged DNA in G1

29
Q

How does p53 work

A
  1. Activated by phosphorylation
  2. Bind to and activates transcription of p21
  3. Enzyme formed by expression of p21 inhibits Cyclin-CDK complexes
    cell cannot continue
30
Q

What amino acids can be phosphorylated by Cdks

A

Serine
Theronine
Tyrosine
Alanine (not phosphorylated by Cdks but can occur in other cellular processes mediated by kinases)

31
Q

Sequence of differentiation of a benign tumour becoming malignant

A

Hyperproliferation > adenomatous polyps> severe dysplasia > adenocarcinoma > invasive cancer

32
Q

How is activity of Cyclin-dependent kinases primarily regulated?

A

Cyclin binding and phosphorylation
- cylcins bind to Cdks to activate them
- phosphorylation of Cdks by CAKs further regulates activity through cell cycle

33
Q
A