L18

Question 1

what needs to happen to carry out a cell cycle

Answer 1

Chromosomes need to be duplicated

Other organelles need to copied

Cells need to grow

Chromosomes need to be segregated accurately

Cell needs to physically divide

Question 2

what are the cell cycle steps

Answer 2

G1: Gap 1

S: Synthesis

G2: Gap 2

M: Mitosis

G0: resting state

Question 3

which steps are the interphase

Answer 3

G1

S

G2

Question 4

what happens in G1

Answer 4

In the cell cycle

• Deciding if conditions are right for a full cell cycle
• Growing and preparing for DNA synthesis

Question 5

what happens in S phase

Answer 5

Replicating DNA and centrosomes

Question 6

what happens in G2

Answer 6

Deciding if conditions are right for mitosis

Question 7

what happens in mitosis

Answer 7

Chromosome segregation and cytokinesis

Question 8

what happens in G0

Answer 8

Cells not in the cell cycle
- Terminally differentiated cells
- Quiescent cells (might divide)
- Senescent cells (never divide)

Question 9

What drives the cell cycle?

Answer 9

Cyclin-dependent kinases (Cdks)

Question 10

what are the features of Cyclin-dependent kinases (Cdks)

Answer 10

Protein kinases that transfer a phosphate onto their substrates

Act as “master regulators”

Have multiple target proteins to control numerous processes in the cell cycle

Cdks have little activity by themselves,
but they are activated by Cyclin proteins

Cyclins also influence the substrate specificity of Cdks

Question 11

when are Cdks fully active

Answer 11

when cyclin, phosphatase, and Cdk-activating kinase (CAK) bind the Cdk

Question 12

give an example of Cdk inhibitors CKIs

Answer 12

p27

Question 13

How can we study cell cycle in mutant cells?

Answer 13

Temperature sensitive (ts) mutants

Mutations that allow gene products to function at low temperature, but not higher temperature

Track cell cycle by size and budding

Question 14

What makes Cyclin levels oscillate?

Answer 14

Cyclin synthesis

Control of Cyclin destruction

Question 15

how is cyclin synthesis maintained

Answer 15

changes in transcription and translation rate, which vary depending on cell type

Question 16

give an example for the Control of Cyclin destruction

Answer 16

degradation of M-Cyclin is triggered by the APC/C

Question 17

how does APC/C signal degrade M-Cyclin

Answer 17

The APC/C is a ubiquitin ligase

It covalently attaches the small protein Ubiquitin to client proteins such as M-Cyclin

Question 18

what are checkpoints

Answer 18

Checkpoints are monitoring systems that check if conditions are right before allowing the next phase to occur

Question 19

how do checkpoints work

Answer 19

Checkpoints act by promoting Cdk activation or inactivation

Question 20

what do mitogens do

Answer 20

promote G1/S-cyclin synthesis (the start of the cell cycle)

Question 21

what does DNA damage do to cyclins

Answer 21

inhibits cyclin activity by phosphoregulation or CKI

Question 22

what prevents M-cyclin destruction

Answer 22

unattached chromosomes

Question 23

where are checkpoints located

Answer 23

G1-S

G2-M

Metaphase-Anaphase

Question 24

what happens in G1-S transition (START, Restriction Point, or G1 checkpoint)

Answer 24

The checkpoint asks:

Are nutritional conditions suitable? (particularly in single cell organisms)

Is the cell receiving proliferation signals? (particularly in multicellular organisms)

Has any DNA damage been repaired?

Was the previous mitosis too long?

Once passed, the cell is committed to the entire cell cycle

Question 25

what happens in G2-M transition (G2 checkpoint)

Answer 25

The checkpoint asks:

Is DNA replication complete?

Has any DNA damage been repaired?

Is the cell big enough (yeast)?

Question 26

what is Rad9 mutant yeast

Answer 26

mutant yeast that do not delay in G2 after DNA damage and they continue to proliferate with damaged DNA and eventually die

Question 27

Rad9 is part of a checkpoint response, not part of the DNA repair response

Answer 27

true

Question 28

what happens in Metaphase-Anaphase transition (Mitotic or Spindle Assembly Checkpoint, SAC)

Answer 28

The checkpoint asks:

Are chromosomes (properly) attached to the spindle?

Once the checkpoint is satisfied:

The APC/C is activated to degrade M-Cyclin

The cells exit metaphase into anaphase

Question 29

when can cell cycle damage not be corrected

Answer 29

• extensive DNA damage
• trial and error correction of chromosome attachments takes too long

Question 30

what happens to the cell cycle when damage cannot be fixed

Answer 30

Either:

Cells can withdraw from the cell cycle (senescence)

• Terminal exit from cell cycle
• Allows cell to remain part of tissue but it will not proliferate

Or:
Cells can undergo programmed cell death (apoptosis)

• Removes cell from organism

Question 31

how do Checkpoints that don’t operate properly result in disease

Answer 31

1. Aberrant mitogen signalling can inappropriately drive cells through the G1 checkpoint into the cell cycle

e.g. Cancer cells overexpressing EGF Receptors (EGFR, HER2), or with mutations in their signalling pathways (eg Ras mutants)

2. Defects in the G2 checkpoint can allow proliferating cells to accumulate DNA damage

e.g. p53 mutations

3. Defects in the mitotic checkpoint can cause aneuploidy (wrong number of chromosomes)

e.g. BubR1 mutation causing cancer predisposition syndrome (MVA)