Lecture 18 -cell Cycle

Question 1

What is a cell cycle

Answer 1

A series of events that need to tAke place for the cell to divide and its content to duplicate

Question 2

How many phases are in the eukaryotic cell?

Answer 2

4

Question 3

What are the phases of cell didvisionnin euk cells?

Answer 3

G1
S -DNA replicates
G2
M- mitosis + cytokinesis

Question 4

Which phase takes the longest and how much

Answer 4

Interphase take 90% of time

Question 5

Cells that are stuck at the end of G1 phase are called…

Answer 5

Cells in G0 state ( arrest stage)

Quiescent

Question 6

What are the 3 cell cycle groups

Answer 6

1- cells that enter a permanent G1 phase (Arrest stage )
Once differentiated Remain in this stage untill they die
2- cells that don’t divide normally but can be induced
3- cells that divide regularly

Question 7

Most cells fall in which type of category?

Answer 7

Mostly cells are in G0 state but most of them can re enter the cell cycle when it needs to divide

Question 8

What determines how much time the whole cell cycle will take

Answer 8

The amt of time taken by the interphase

Question 9

Whats the main thing happening in G1 phase?

Answer 9

Cell grows and carries out normal metabolism

Organelles duplicate

Question 10

S ( synthesis)

Answer 10

DNA and chromosome duplication

Question 11

What happens in G2 phase?

Answer 11

Cell grows and prepares for mitosis

Question 12

What happens in M phase?

Answer 12

Mitosis/ karyokinesis

Cytokines

Question 13

What is required to move on to the next stage

Answer 13

Cell signalling

Question 14

What signals the cells in Go to divide , what initiates the cell cycle?

Answer 14

Ras signalling of MAP kinase cascade triggered by RTK receptor

Question 15

How does the RTK triggers or speeds cell division

Answer 15

1- MAP kinase cascade triggered by RTK
2- cells produce Epidermal growth factor
2- this trigger stem cells and other cells
4- this signalling pathway turn on the transcription of specific genes , Eg cyclins , this speeds up cell division

Question 16

Cell cycle control system is similar in euk

Answer 16

True

Question 17

CELL CYCLE CONTROL SYSTEM

————- is like the black box in the cell

Answer 17

Cell cycle control.

Question 18

What are the major components of the cell cycle control system?

Answer 18

1- cyclins

2- cyclin dependent protein kinases ( cdks)

Question 19

How does the cell cycle control system work ?

Answer 19

The cell control cycle has brakes or checkpoint to arrest the cell cycle
If a stage is incomplete, the process will come to a stop
Eg- if DNA is damaged , the cell cycle comes to a stop, the DNA is repaired before proceeding

Question 20

Overall Purpose of the cell cycle control system ?

Answer 20

Ensures that the key processes in the cycle occur in the proper sequence

Question 21

Maturation promoting factor is a complex of

Answer 21

Cdk 1 + cyclin B

Question 22

Role of cyclin in maturation promoting factor- MPF /M cdk ( cyclin B + cdk)

Answer 22

• regulates cdk activity
• levels rise and falls throughout
• helps direct the cdk to the target proteins that the cdk phosphorylates

Question 23

Role of cdk in maturation promoting factor

Answer 23

• a kinase protein that adds a phosphate from ATP to other proteins , to modify target protein

Question 24

How does Progress to the M phase occur?

Answer 24

-Cdk+ cyclin = enzymatically active (M cdk)
-cdk is phosphorylated at 2 adj sites by inhibitory kinase wee1
-wee1 keeps it inactive until cdc25 phosphatase removes the phosphate
The complex the:-
- The cyclin also helps direct the cdk to the target proteins that the cdk phosphorylates
- cyclin helps cdk enzymic activity

Question 25

Level of cyclin during and btw stages

Answer 25

Entering mitosis - increasing towards the highest point Mitosis- highest point Leaving mitosis- steep fall and 0 before leaving Entering interphase - 0 Interphase - 0 right in beg , then gradually increasing Leaving interphase - gradually to increase

Question 26

What regulates the activity of cdks

Answer 26

Accumulation of cyclin

Question 27

Formation of cyclin - cdk complex drives entry to what stages

Answer 27

S phase and M phase

Question 28

What helps in the formation of active M cyclin - cdk complexes

Answer 28

Increasing concentration of relevant cyclin called - M cyclin ( cyclin B)

Question 29

What happens when enough MPF is triggered ?

Answer 29

It triggers mitosis - prepares chromosome for degradation by phosphorylates H1 histones - causes DNA to condense - activates micro tubules proteins to assemble the mitotic spindles - shutdown Wee1 and promote production of mcdk - when an mcdk is activated it phosphorylates more cdc25 which then removes phosphate from mcdk , activating it POSITIVE FEEDBACK LOOP

Question 30

Overall what determines if the cell cycle will transition from one phase to another

Answer 30

Cyclin / cyclin Cdk complex Eg Mcdk G1/ Scdk Scdk

Question 31

What drives entry to S phase through G1 phase

Answer 31

Active G1/S cdk phosphorylates regulatory proteins that activate transcription of genes required for DNA replication

Question 32

What drives entry to M phase

Answer 32

When the M cdk complex is active , the cdk can phosphorylate a different set of regulatory proteins

Question 33

How is cyclin concentration regulated? | Hint- how is the amount of any protein regulated

Answer 33

Regulated by ubiquitin medated degradation | Uniquitin tags S or M cyclin for degradation in proteosome

Question 34

As said earlier whta regulates cdk activity

Answer 34

Cyclin | Eg cyclin degradation inactivates cdk

Question 35

What regulates cyclin - cdk

Answer 35

Kinases and phosphatase regulate activation and inactivation And cyclin regulates formation

Question 36

How is M cdk activated?

Answer 36

- once the M cyclin cdk is active - it is phosphorylated at 2 adj sites by an inhibitory protein kinase called wee1 - this this keeos the M cyclin cdk inactive untill - phosphatase Cdc25 removes these phosphates

Question 37

Wee 1 is part of checkpoint , what does it check ?

Answer 37

Checks if cell is big enough for mitosis

Question 38

Activity of cdk can be blocked by 2 methods , state them ?

Answer 38

- phosphorylation by inhibitory kinase wee1( discussed earlier) - also be blocked by cdk inhibitors (p27)

Question 39

How do cdk inhibit cdk activity⁉️⁉️

Answer 39

- Cdk inhibitory protein (p27) binds to an active cyclin cdk complex - attachment prevents the cdk from phosphorylating target proteins required for progress through G1 inti S phase

Question 40

Jist like wee1, cdk inhibitors are also part of checkPoint . What do they check

Answer 40

Check if envr conditions are favourable | Also gives more time for cells to grow

Question 41

What happens DNA replication not complete or DNA damage during S or G2 phase

Answer 41

cdc25 removed phosphate from M cdk ( activating it) ,allowing it to progress through mitosis. When DNA is damaged , Inhibition of activating phosphatase Cdc25 , Blocks entry to mitosis- part of G2 checkpoint

Question 42

What happens if Chromosomes not attached to spindles

Answer 42

Inhibition of APC/C activation delays exit from mitosis

Question 43

What happens if Environment not favourable in G1 G2

Answer 43

``` Cdk inhitors (p21) inhibit S- cdk , block entry to S phase Cdc25 inhibited, preventing activation of mcdk ```

Question 44

What promotes the production of cyclin that stimulate cell division

Answer 44

Mitogens Mitogens turn on cyclin genes by activating cell signalling pathways Absence of mitogens causes the cell to arrest in G1 or G0

Question 45

What promotes cell proliferation and how ?

Answer 45

Mitogens , by inhibiting the Rb protein - In the absence of mitogens, de phosphorylated RB proteins holds specific transcription regulators in an inactive state - Mitogens binds to the cell surface receptors activate intracellular signalling pathways that lead to the formation and activation of G1- cdk and G1/ s - cdk complexes - these complexes phosphorylate and thereby inactivate , the Rb protein , releasing the transcription regulators needed to activate the transcription of genes / cyclins required for entry in S phase

Question 46

Which transition itself is a critical checkpoint

Answer 46

G1 -> S phase

Question 47

What is like a 4 way stop ?

Answer 47

G1 to s phase

Question 48

What are the things that can happen in the g1 to s transition

Answer 48

1- cell can commit to completing another cycle 2- cells can withdraw temporarily until conditions are right 3- withdraw from cell cycle and enter g0 , either temp or permanently in case of terminally differentiated cells

Question 49

Then what exactly decides what to do out of these 3

Answer 49

Intracellular and extracellular signals decide if the cell proceeds to S phase or G0 phase

Question 50

We saw that s cdk and m cdk is 0 at G1 phase , how does this happen

Answer 50

S cdk and M cdk are inactive in G1 - by eliminating all existing cyclins - block the synthesis of new cyclins - recruit cdk inhibitor proteins

Question 51

What happens if DNA is damaged in G1

Answer 51

DNA damage can arrest cell cycle in late G1 ( G0 arrest phase) - kinase work by activating Tp53 and haling its rapid degradation - activated p53 accumulates and stimulates the transcription of the gene that encodes the cdk inhibitor protein p21 P21 binds to G1/ S- cdk and S-cdk and inactivates them , so the cell cycle arrests in G1

Question 52

3 ways cell enter non dividing stages

Answer 52

1- cells can delay progression through cell cycle until conditions become favourable or until DNA damage is fixed 2- cells can also withdraw from cell cycle permanently ( terminally differentiated cells) - cyclin and cdk genes permanently shut down - eg muscle cells, nerve cells 3- cells can withdraw from cell cycles temporarily - enter into G0 until stimulated to proliferate

Question 53

Cell division rate depends on

Answer 53

The time soent in g0 and G 1 phase

Question 54

Role of S cdk in S phase

Answer 54

- initiates DNA replication and blocks re replication | Activates helicase and recruits other proteins like (Cdc6) to the replication fork

Question 55

Cyclin concentration is regulated by

Answer 55

Ubiquity medial degradation Or Transcription genes activated by mitogens or RAS signalling