Cell Cycle

Question 1

What are the 2 main phases of the cell cycle? What makes them up?

Answer 1

interphase: G1, S, G2

mitosis

Question 2

What are the 4 checkpoints?

Answer 2

1. G1/S: start or replication point: committed to undergo replication
2. G2/M: has all DNA been replicated?
3. Metaphase/Anaphase: attached to mitotic spindle?
4. DNA damage monitoring

Question 3

What are all the cyclins?

Answer 3

Mid G1: Cyclin D/CDk 4
            Cyclin D/CDK6
Late G1: Cyclin E/CDK2
S: Cyclin A/CDK2
M: Cyclin A/CDK1
Cyclin B/CDK1

Question 4

Growth factor signaling pathway. YOU GOT THIS :)

Answer 4

1. EGF binds to transmembrane receptor protein
2. receptor dimerizes and autophosphorylates itself adding P to tyrosine residues
3. continued phos; phosphotyrosine residues form docking sites and GRB2 binds here
4. GRB2 links with Sos
5. Sos activates G-protein Ras
6. Ras activates Raf
7. Raf activates MAP kinase kinase (MEK)
8. MEK activates Map kinase
9. Map kinase translocates to the nucleus
10. regulates transcription of genes and stimulates transcription of c-Fos

Question 5

What is the end result of EGF growth factor signaling?

Answer 5

c-Fos transcription

Question 6

What does Map kinase mediate its effects?

Answer 6

In the nucleus

Question 7

What is Sos?

Answer 7

a guanine nucleotide exchange factor

Question 8

Regulation of G1/S transition

Answer 8

1. C-fos –> transcription of cyclinD/CDK4/6
2. Rb/E2F is inactive, but CycD/CDK4/6 phos Rb, and released E2F
3. E2F is free to activate cyclin A/CDK2 and cyclin E/CDK2
4. CyclinE/CDK2 is inactive and is phosphorylated by cdc25A
5. Cyclin A/CDK2 is also inactive and complexed with p27KIP1, and gets phosphorylated in late G1 by CyclinE/CDK2
6. Cyclin A/CDK2 promotes DNA replication/phosphorylation of components of the ORI complexes

Question 9

What is CycE/CKD2 complexed with in it’s inactive state?

Answer 9

cdc25A

Question 10

What is CycA/CDK2 complexed with in it’s inactive state?

Answer 10

p27kip1

Question 11

Once CycA/CDK2 promotes DNA replication/phosphorylation of ORI complexes, what happens?

Answer 11

1. cdc25C is activated at completion of replication
2. ATM senses replication forks
3. Cdc25C dephosphorylation activates cyclinA/B CDK1
4. assembly of mitotic spindle
5. anaphase is delayed until chromosomes are attached to mitotic spindle; correct assembly activates Anaphase Promoting Complex (APC) allowing
6. APC –> ubiquitinaton of cohesion;Cyc A/cyc B CDK 1 are inactivated
7. cell exits mitosis; dephs of cyclin cdk targets by cdc14

Question 12

What is the main goal of c-fos signaling? What does it activate?

Answer 12

Cyc A/CDK2-promotes DNA replication

Question 13

DNA damage activated what 2 things?

Answer 13

ATM: activated by double stranded breaks
ATR: activated by UV light/DNA-damaging drugs

Question 14

ATM and ATR prevent activation of what 2 things?

Answer 14

cyclin-CKD1–> S phase

cyclin-CDK2-> mitosis

Question 15

Explain ATM/ATRs rule with p53?

Answer 15

1. phosphorylation of p53
2. stabilization of p53
3. upregulates p21cip1
4. inhibiting CDK2/CDK1; and cannot transition from G1/S or G2/M

Question 16

What is the disease in which ATM is mutated and can’t react to double strand breaks?

Answer 16

ataxia telangiectasia

Question 17

P53 pathway with apoptosis?

Answer 17

1. ATM/ATR stablize p53
2. p53 causes PUMA and BID to act on BCl-2(which is inhibiting Bax)
3. bAx activated, allowing release of cyc C from the mitochondria into the cytoplasm
4. cyc C binds to Apaf-1
5. triggers oligomerization –> apoptosome
6. activates cap 9
7. activates cap 3
8. cell death