regulation of the 3rd checkpoint

Question 1

3rd checkpoint

• name
• enters into?

Answer 1

metaphase-to-anaphase transition

re-entry into G1

Question 2

3rd checkpoint

- role

Answer 2

detects chromatin attachment problems

normal timing of anaphase

.:. can block cell cycle

Question 3

APC/C

• means
• function
• type of enzyme

Answer 3

anaphase promoting complex

targets cyclins for degradation

an E3 ubiquitin ligase

Question 4

how is APC/C activity controlled?

upstream regulation

Answer 4

activation:
M-Cdk phosphorylates APC/C
-> then can Cdc20 bind

inactivation:
Mad2 binds to Cdc20
- prevents activation

Question 5

APC/C triggers entry into anaphase

Answer 5

M-Cdk phosphorylates APC/C

->

Question 6

APC/C triggers entry into anaphase

Answer 6

M-Cdk + Cdc20 activate APC/C

• > ubiqutination of securin
• > degraded
• > separase released
• > cleaves cohesion
• > sister chromatids pulled apart by spindle fibres

Question 7

Mad2 checkpoint break

Answer 7

blocks anaphase entry via APC/C inhibition

- until every chromatid is attached to a spindle

Question 8

Mad2

• recruited
• sequestered

Answer 8

to unattached kinetochore

sequesters + inhibits Cdc20

Question 9

mitotic exit

- requires

Answer 9

reversal of early mitotic events induced by M-Cdk

Question 10

nuclear envelope formation

Answer 10

requires destruction of M-cyclins

-> M-Cdk cannot induce degradation of nuclear pore complex + nuclear lamina

Question 11

APC/C targets M and S-cyclins for destruction

Answer 11

active APC/C + E1 + E2 add ubiquitin molecules onto cyclin of M-Cdk + S-Cdk
-> target for degradation

drastic decrease in active M-Cdk

• ve feedback loop established
• > active APC/C decreased due to decrease in active M-Cdk (normally phosphorylated APC/C)

Question 12

when are S-cyclins + M-cylins degraded?

Answer 12

S
= start of mitosis

M
= metaphase to anaphase transition

Question 13

actin-myosin ring drives cytokinesis

Answer 13

begins in anaphase

completed in telophase

Question 14

regulators of metaphase-anaphase transition

Answer 14

Cdc20

• regulatory protein binds to APC/C
• promotes

APC/C

• ubiquitin ligase
• promotes

Securin

• inhibitory protein binds separase
• blocks

Separase

• protease
• promotes

Mad2

• regulatory protein binds Cdc20
• blocks

Question 15

re-entry into G1 depends on APC/C activation by Cdh1

Answer 15

M-Cdk inhibits formation of Cdh1-APC/C complex
by phosphorylating Cdh1

destruction of M-cyclin via ubiquitination
-> Cdh1 is dephosphorylated
-> binds to APC/C
= active

Question 16

p27

Answer 16

a CKI

binds + inactive cyclin-Cdks

Question 17

p27 contributes to G1 stability
- mechanism

• effects

Answer 17

acts in G1
- blocks G1/S-Cdk and S-Cdk activity

> maintains G1
prevents cell cycle progression
levels elevated in mitogen-starved cells

Question 18

how is p27 inactivated in order to pass Start checkpoint?

Answer 18

G1-Cdks remove p27 from G1/S-Cdks

p27 then phosphorylated by Cdks
-> SCF ubiquitin ligase tags for degradation in proteasome

-> p27 can no longer act as block on S-Cdk either

Question 19

G0

- entry into G0 process

Answer 19

INK4 proteins contribute to cell entering G0

absence of mitogens

• > INK4 proteins act as CKIs
• > block G1-Cdk function
• > high levels of Rb
• > cell enter resting phase

ALSO:
G1-Cdk cannot enter nucleus to phosphorylate its targets needed for cell cycle progression

Question 20

G0

- presence of mitogens

Answer 20

e.g. Myc

directly lowers expression of INK4 proteins
-> G1-Cdk is active

-> cell cycle progression