Lecture 10 - The cell cycle

Question 1

When does DNA replication occur

Answer 1

before mitosis in the S phase

Question 2

what does the M phase consist of

Answer 2

both mtosis and cytokinesis

Question 3

start transition

Answer 3

is the environment favourable?

Question 4

G2/M transition

Answer 4

is all dna replicated?
is environment favourable?

Question 5

metaphase to anaphase transition

Answer 5

are all chromosomes attached to the spindle?

Question 6

checkpoints

Answer 6

ensure conditions are suitable for division

Question 7

how are checkpoints mediated

Answer 7

by the controlled activity of cyclin-dependent kinases

Question 8

what do cdks do

Answer 8

they phosphorylate target proteins for the cell cycle to progress

Question 9

what do cdks require

Answer 9

cyclins

Question 10

when are cdks present

Answer 10

can be present throughout all cell cycel stages

Question 11

when do cyclins and cdks work

Answer 11

one cdk may work with multiple cyclins,

Question 12

degradation of cyclins

Answer 12

cyclins can be ubiquinated
polyubiqtylation marks cycline for degradtion by the proteasome
If cyclins are broken down CDKs will no loner be active

Question 13

what promotes M cyclin degradation

Answer 13

APC/C and Cdc20

Question 14

What do APC/C and Cdc20 act as

Answer 14

They act as an E3 ubiquitin ligase

Question 15

What are CDKs activated by

Answer 15

cyclins (by exposing T loop) and Cdk-Activating kinase (Once T loop is exposed CAK can hosphorylate Cdk to further actuvate it)

Question 16

what reverses the effect of cyclin cdks

Answer 16

protein phosphatases (PP2A) remove phosphorylation from proteins
thye usually have same targets as cyclin-cdks

Question 17

what particpates in a complex feedback loop

Answer 17

PP2A and M-CDK participate in a complex feedback loop

Question 18

what happen before m phase

Answer 18

1. PP2A is active
2. PP2a desphosphorylates M-CDK targets to stop progession into mitosis

Question 19

what happens during m-phase

Answer 19

1. M cyclin is produced
2. M CDK is active
3. M Cdk indirectly inhibits PP2A activity
4. M cyclin phosphorylates its target to promote mitosis progression

Question 20

how can cyclin-cdks be inactivated

Answer 20

1. cdk inhibitor proteins (CKI) binds cyclin cdks
   CKIs disrupt the Cyclin-cdk interaction which inactivates the cdk
2. phosphorylation
   the inhibitory phosphorylation is at a different site from the activating phosphate added by Cak

Question 21

examples of cdk inhibitor proteins

Answer 21

p27 and p21

Question 22

Wee 1 kinase

Answer 22

can add an inhibitory phosphorylation

Question 23

Cdc phosphatase

Answer 23

remove inhibitpry phosphorylation

it must be phosphorylated to be active

Question 24

positive feedback loop to ensure cyclin-cdk activation

Answer 24

1. active m-cdk acivates its activators (Cdc25 phosphorylaton)
2. Active M-CDK inhibits its inhibitors- PP2A phosphatase inactivation, Wee 1 kinase phosphorylation

Question 25

how can cells be retained in G1

Answer 25

Rb inhibition of E2F
E2F is a transcirption factor required for S phase gene expressiin
Rb can be inhibited by phosphorylation

Question 26

Mitogens

Answer 26

trigger production of cell cycle protein myc

Question 27

what do mitogens activate and then what do they upregulate

Answer 27

they activate a signaling pathway including RTKs, Ras, and a MAP kinase cascade
these upregulate the epression of Myc

Question 28

Myc

Answer 28

key transcription factor involvd in cell cycle control

Question 29

how does myc help with the inhibition of rb

Answer 29

1. Myc activates G1 cyclin gene expression
2. G1-Cdk phosphorylates Rb
3. Phosphorylated Rb releases E2F
4. E2F activates expression of S-phase genes

Positive feedbacj through:
1. E2F aactivation
2. G1/S Cdk and S-Cdk phosphorylation of rb

Question 30

how does DNA damade blobk cells cycle progression via CKI synthesis

Answer 30

1. DNA damage induces p53 transcription factor activation
2. p53 activates p21 expression
3. p21 is a CKI that inhibits G1/S-Cdk and S-Cdk