WEEK 2 Flashcards

1
Q

What is cell proliferation?

A

the process by which a cell grows and divides to produce two daughter cells, leads to exponential increase in cell number

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2
Q

What is the fundamental basis of cell proliferation?

A

New cells must be identical therefore growth and division process (cell cycle) must be tightly controlled

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3
Q

How is the cell cycle controlled?

A

Checkpoints and feedback control

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4
Q

Give the stages of the cell cycle

A

G1 phase->growth and preparation for DNA replication
S (synthesis) phase->DNA replication
G2 phase->growth and preparation for mitosis
M (mitosis) phase->chromosome segregation, cell division, cytokinesis

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5
Q

What is cytokinesis?

A

Cytoplasmic division after mitosis, forming 2 daughter cells with similar amount of nuclear DNA and organelles

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6
Q

What are cell cycle checkpoints?

A

Critical control points where stop and go-ahead signals can regulate the cell cycle

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7
Q

What are the three major checkpoints?

A

G1, G2 and M checkpoints

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8
Q

Describe the G1 checkpoint (restriction point)

A

ensures cell is large enough and contains enough nutrients to divide. if cell doesn’t receive go-ahead signal at this point, it will exit the cell cycle and switch to a non-dividing state (G0)

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9
Q

Describe the G2 checkpoint

A

ensures DNA replication in S phase is completed successfully

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10
Q

Describe the Metaphase checkpoint

A

ensures all chromosomes are attached to mitotic spindle by a kinetochore

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11
Q

What occurs if there’s failure at any of these checkpoints?

A

Apoptosis-induced cell death

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12
Q

What enzymes regulate the cell cycle?

A

Cyclin-dependent kinases (CDKs)-G1, G2 and M CDKs

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13
Q

How are CDKs activated?

A

Phosphorylation due to Cyclin binding-a molecule which’s fluctuations indicate a need for new cells in a specific area

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14
Q

How do CDKs regulate the cell cycle?

A

They activate and encourage the continuation of the cell cycle to proliferation

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15
Q

What is a kinase?

A

A protein which activates or deactivates another protein by phosphorylating them

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16
Q

When do cyclins accumulate and what effect does this have on mitosis?

A

During G1, S and G2 phases, leading to enough cyclin available by the end of G2 checkpoint to form M-CDK complexes initiating mitosis

17
Q

How does M-CDK switch itself off?

A

Initiating a process which leads to cyclin destruction

18
Q

Which cyclin-CDKs are required at the restriction point?

A

CDK4/cyclin D and CDK2/cyclin E/A

19
Q

Which cyclin-CDKs are required at the Metaphase checkpoint?

A

CDK1/cyclin A/B

20
Q

What regulates the restriction point?

A

Retinoblastoma protein (pRB) which is a tumour suppressor protein

21
Q

How does pRB regulate the restriction point?

A

In absence of growth factors, pRB binds to transcription regulators of genes for cell proliferation, preventing cell cycle continuation
Growth factor presence causes activation of G1 and G1/S CDKs which phosphorylate pRB and cause its release from transcription regulators, activating genes for cell proliferation

22
Q

What regulates the DNA damage checkpoint (G1/S phase)?

A

p53 which is a tumour suppressor protein

23
Q

How does p53 regulate the DNA damage checkpoint?

A

p53 increases due to DNA damage, activating transcription of p21, an inhibitor of CDK, preventing continuation into S phase, giving time for DNA repair

24
Q

What happens if DNA damage is too severe?

A

p53 can induce apoptosis

25
Q

What occurs due to a loss of function mutation?

A

Unrestrained replication of damaged DNA, leading to genomic instability/resistance to apoptosis

26
Q

What are the consequences of checkpoint failure?

A

Proliferation of cells in absence of growth factors, replication of damaged DNA, segregation of incompletely replicated chromosomes, divisions of cells with wrong number of chromosomes->leads to genomic instability and increased rate of mutation

27
Q

Hallmarks of cancer are

A
Sustaining proliferative signalling
Evading growth suppressors
Activating invasion and metastasis
Enabling replicative immortality
Inducing angiogenesis
Resisting apoptosis
28
Q

Stages of a growth factor signalling pathway

A

membrane receptor activation leads to dimerisation and phosphorylation, adapter protein binds to phosphorylated receptor in cytoplasm, Ras (G-protein) binds to adaptor, signalling cascade, phosphorylation of gene regulatory proteins, expression of proliferative genes

29
Q

Define oncogenic

A

pertaining to the origin or development of tumours or cancer

30
Q

What is the result of receptor becoming oncogenic?

A

deregulated cell proliferation due to mutated/constitutively active/over-expressed receptor causing signalling pathway occurrence without presence of growth factor

31
Q

What is the result of signalling proteins becoming oncogenic?

A

deregulated cell proliferation without activation of receptor due to mutated/constitutively active Ras/Kinase proteins

32
Q

What is the result of regulatory proteins becoming oncogenic?

A

deregulated cell proliferation due to over-expression of transcription factors

33
Q

LOOK OVER NOTES ON:

A

Metabolism and its control (1) and Appearance and Classification of Epithelial tissue (+histology)