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PSA712 Biochemistry > Cell Cycle and Division > Flashcards

Cell Cycle and Division Flashcards

1
Q

Give two examples of when and why we would want to control cell growth.

A
  1. Embryogenesis/early growth
  2. Would healing
  3. Menstruation
  4. Immune response to infection
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2
Q

Give two examples of when cell growth and division goes wrong.

A
  1. Hyperplasia
  2. Autoimmune disorders
  3. Premature ageing (progeria)
  4. Cancer
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3
Q

What two general stages occur in the cell cycle?

A
  1. Growth = Interphase

2. Division = Mitotic phase

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4
Q

Interphase can be divided into G1, S and G2. What happens at each point?

A 
G1 = cell is metabolically active and growing.
S = DNA synthesis/replication.
G2 = cell growth continues, proteins are synthesised in preparation for mitosis.
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5
Q

Progression of cells through the division cycle is regulated by both extracellular and internal signals - this are known as what?

A

Control points.

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6
Q

What major control point controls progression from G1 to S.

A

START

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7
Q

Once a cell passes the control point ‘START’ what phase does it enter?

A

S phase - undergo one division cycle.

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8
Q

The restriction point in late G1 functions like ‘START’. Once the cycle has passed this point, the cell proceeds to what phase?

A

S phase

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9
Q

If specific factors are not present in in G1, progression stops and the cell will enter what phase?

A

G0

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10
Q

Progression to M phase is triggered by what?

A

Hormonal stimulation

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11
Q

What are the two cell cycle checkpoints?

A

DNA damage checkpoints (3)

Spindle assembly checkpoint (1)

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12
Q

What happens at the DNA damage checkpoint?

A

Ensured damaged DNA is not replicated and passed on.

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13
Q

What happens at the spindle assembly checkpoint?

A

Stops mitosis at metaphase if chromosomes are not properly aligned on the spindle.

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14
Q

Control mechanisms prevent re-initiation of DNA replication until the cell cycle is complete. What proteins control the cycle?

A

MCM helicase proteins

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15
Q

Explain how MCM helicase proteins function?

A
  1. MCM helicase proteins bind to origins of replication with the origin recognition complex.
  2. Once initiation has occurred, MCM proteins are displaced from the origin so that replication cannot initiate again until after mitosis.
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16
Q

Cell cycle analysis requires what experimental equipment (2)?

A
  1. Flow cytometer

2. Fluorescence-activated cell sorter

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17
Q

DNA content is 2n normally, during S phase, replication increases the DNA content to what?

A

4n

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18
Q

What three studies have helped to understand the triggering of major cell cycle transitions?

A
  1. Studies of frog oocytes (1971)
  2. Genetic analysis of yeasts
  3. Protein synthesis in early sea urchin embryos (1983)
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19
Q

Give a general statement of what happened in the studies of frog oocytes.

A

Oocytes could be induced to enter M phase by microinjection of cytoplasm that has been hormonally stimulated.

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20
Q

What was the cytoplasmic factor responsible for inducing cells to enter M phase in the study of frog oocytes?

A

Maturation promoting factor (MPF).

21
Q

Maturation promoting factor (MPF) acts as a general regulator of G2 -> M phase. It is now known as what?

Cdk and cylin

A

Cdk1/cyclin B

22
Q

Cell division cycle mutants (cdc genes) are required for the passage through what point?

A

START

23
Q

Cdc genes encode for what proteins?

A

Protein kinases.

24
Q

Protein kinase has been shown to be a cell cycle regulator conserved in all eukaryotes. What is it now know as in cdk form?

A

Cdk1

25
Q

Microinjection of what cyclin is sufficient to trigger the G2 -> M transition.

A

Cyclin A

26
Q

Structure of MPF consists of what two molecules bound to each other?

A

Cyclin B and Cdk1

27
Q

Regulation of MPF occurs how?

refer to cdk1

A

Phosphorylation and dephosporylation of cdk1.

28
Q

Cyclin B and cdk1 (collectively forming MPF) is inactive when?

A

cdk1 is phosphorylated and inhibits MPF.

29
Q

Cyclin B and cdk1 (collectively forming MPF) is active when?

A

Cdk1 is dephosphorylated and MPF is active - allowing cell to move from G2 and enter M phase.

30
Q

During G1, what cyclin and cdk are present?

A

Cyclin D

Cdk4 / Cdk6

31
Q

During G1 what cyclin and cdk are present?

A

Cyclin E

Cdk2

32
Q

During S phase, what cyclin and cdk are present?

A

Cyclin A

Cdk2 / Cdk1

33
Q

During M phase, what cyclin and cdk are present?

A

Cyclin B

Cdk1

34
Q

What cdk can substitute for all other cdks?

A

Cdk1

35
Q

The activity of cdks is regulated by what four mechanisms?

A
  1. Association of cdks and cyclin partners.
  2. Activation of cdk/cyclin complexes requires phosphorylation of threonine at position 160.
  3. Inhibitory phosphorylation of tyrosine near the cdk amino terminus, catalysed by Wee1 protein kinase.
  4. Binding of inhibitory proteins (cdk inhibitors).
36
Q

State two types of cdk inhibitors.

A
  1. Ink4 family - p15, p16, p18 etc

2. Cip/Kip family - p21, p27, p57 etc

37
Q

Through what pathway is cyclin D1 synthesised?

A

RAS pathway.

38
Q

Cyclin D1 complexes through which point?

A

Restriction point in the cell cycle.

39
Q

Describe what happens in the RAS pathway.

A
  1. Growth factor binds to receptor tyrosine kinase (RTK).
  2. RTK phosphorylates RAS.
  3. RAS phosphorylates RAF.
  4. RAF phosphorylates MEK.
  5. MEK phosphorylates ERK which enter the nucleus and binds to DNA, promoting transcription of cyclin D1.
40
Q

Defects in cyclin D1 regulation could contribute to the loss of growth regulation which is a characteristic of what type of cells?

A

Cancer cells.

41
Q

Rb is the prototype of a tumour suppressor gene. Inactivation causes what?

A

Tumour development.

42
Q

ATM/ATR activate a signalling pathway that leads to cell cycle arrest, DNA repair and sometimes programmed cell death. ATM and ATR recognise what?

A
  1. ATM - recognises double strand breaks.

2. ATR - recognises single stranded breaks or unreplicated DNA.

43
Q

ATM and ATR phosphorylate what two checkpoint kinases?

A

Chk1 and Chk2.

44
Q

Chk1 and Chk2 phosphorylate and ihibit Cdc25 phosphatases, which are required to activate what molecules?

A

Cdk1 and Cdk2.

45
Q

Inhibition of cdk1 arrests the cell cycle at what position?

A

Arrest in G2.

46
Q

Inhibition of cdk1 arrests the cell cycle at what point?

A

Arrest in G1 and S.

47
Q

How is the cell cycle regulated by cyclins? Briefly describe the mechanism of control

A

Cyclins are required for cyclin-dependent kinases (Cdks) to exert their kinase activity. Their presence in the cell during the cell cycle is governed by their cyclical synthesis and degradation. During interphase, they are synthesised as needed, then during M-phase they are targeted for degradation by ubiquitination (tagging with multiple ubiquitin molecules which signals for them to be degraded by the proteasome).

48
Q

What is the function of the centromere?

A

To provide a foundation for the formation of the kinetochore.

PSA712 Biochemistry (11 decks)

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