Cell Proliferation & Division

Question 1

Why do cells need to divide?

Answer 1

To allow for embryogenesis

Growth and repair of damaged tissue

Question 2

Whats a Mitogen

Answer 2

Signal protein stimulates cell division by overcoming intercellular braking mechanism.

Question 3

What are Growth factors?

Answer 3

signal proteins that stimulate cell growth by promoting the synthesis of proteins and other macromolecules

Question 4

Why must the cell cycle be controlled?

Answer 4

maintain genome integrity

prevent deregulated cell division

Question 5

Give an overview of the cell cycle include the checkpoints

Answer 5

G1
G1 checkpoint
G1/S checkpoint
S
G2
G2checkpoint
M phase (Mitosis and Cytokinesis)
Metaphase checkpoint

Question 6

G1, What happens?

Answer 6

Cell increases in size and mass

cell prepares for DNA replication

Question 7

G1 checkpoint, what is it

Answer 7

G1 checkpoint or Restriction point
checks cell is large enough to divide and nutrients for DNA replication and to support daughter cells are sufficient
If not cell enters G0 quiescence phase

Question 8

How is the G1 checkpoint controlled?

Answer 8

Growth factor binds to cell stimulates cell proliferation
increase G1 cyclins –> bind to specific Cdk forming active G1-Cdk complex
phosphorylates retinoblastoma protein (pRB)
causes it be realised from transcription factor to which it was bound
activates genes for cell proliferation

Question 9

in the absence of growth factors what is the function of pRB

Answer 9

Retinoblastoma protein binds to transcriptional regulators preventing the transcription of proteins that would stimulate cell division.
Prevents uncontrolled cell division

Question 10

G1/S checkpoint, when does it occur what is it?

How is it regulated

Answer 10

-At end of G1 phase
-Ensures there is no damage to the DNA
-p53 tumour suppressor gene regulates this phase
if there is damage in DNA [p53] increases –> transcription regulator so activates transcription o fp21 a Cdk inhibitor binds to G1-Cdk’s and G1/S Cdk’s. prevents continuation into S phase
Allows p53 to repair small amounts of DNA damage
if lots of damage p53 triggers apoptosis

Question 11

G2 phase, what is it what happens?

Answer 11

2nd growth phase
increase in the number and synthesis of organelles 
energy stores are increased
further increase in size and mass
spindle fibres start to form

Question 12

S phase

Answer 12

DNA replication via semiconservative replication (2 copies of each chromosome x shape)

Question 13

G2 checkpoint, what is it?

Answer 13

occur at the end of the G2 phase
checks DNA has been replicated successfully
cell is of correct size to enter M phase
is cell is not or DNA is damaged halted –> apoptosis

Question 14

What happens at G2 that drives the cell into the M phase

Answer 14

Throughout G1,S and G2 [M cyclin] has been increasing and M cylcin-Cdk complexes have been forming, however remain inactive.
At the end of G2 they are activated by phosphatase Cdc25 that removes inhibitory phosphates on M-Cdk triggers more M-Cdk activation positive feedback
M-Cdk helps to prepare chromosomes for segregation and induces assembly of mitotic spindle
drives cell into mitosis

Question 15

M phase

Answer 15

Mitosis nuclear division and segregation of sister chromatids to form ideal daughter chromosomes.
splitting of cytoplasm and organelles via cytokinesis

Question 16

Metaphase checkpoint, what is it? why is this significant in preventing uncontrolled proliferation?

Answer 16

ensures chromosomes are attached to mitotic spindle correctly
if not cell cycle halted–> apoptosis

Once cell passes this point M-Cdk is switched off. Anaphase promoting complex marks M-cyclin with ubiquitin chain –> attracts proteasomes which hydrolyse m cyclin. Cdk inactivated. Prevents cell immediately going into another cycle.

Cdk remain in cell until next cell cycle wher more M-cyclin will be produced

Question 17

What is apoptosis?

Answer 17

programmed cell death.

cell breaks down from the inside–> forms apoptotic bundles which are engulfed by macrophages

Question 18

What is Necrosis?

Answer 18

Unregulated cell death, due to trauma or bacterial infection

involves csm rupturing release of hydrolytic enzymes

Question 19

What happens if p53 is mutated?

Answer 19

loss of function

uncontrolled cell proliferation and replication of damaged DNA

genome instability and resistance to apoptosis
the more unstable the genome the higher the mutation rate higher chance of cell becoming cancerous

Question 20

Outline a growth factor singling pathway

Answer 20

ligand binds to receptor
activation via phosphorylation
Ras protein (a G-protein activated) triggers a kinase cascade
eventually a molecule enters the nucleus and activates gene regulatory proteins phosphorylating them causing release form DNA allowing expression of genes required for cell proliferation

Question 21

Scenarios involving singling pathway that can lead to deregulated cell proliferation

Answer 21

Oncogenic receptors –> constant activation

Oncogenic singling proteins –> mutated Ras activates pathway without binding of growth factor

Oncogenic regulatory proteins–> leads to over expression of transcription factors on DNA