15. Regulation Of The Cell Cycle In G1,S

Question 1

G1 phase roll

Answer 1

Transcriptional reprogramming and intense protein synthesis, preparing to replicate

Question 2

S phase roll

Answer 2

Doubling of 23 pair chromosomes

Question 3

G2 phase roll

Answer 3

Restricting mitosis until DNA is doubled completely and cell becomes big enough

Question 4

M phase roll

Answer 4

Mitosis (prophase, prometaphase, metaphase, anaphase, telophase)

Question 5

Difference between Quiescent G0 and Senescent G0

Answer 5

Quiescent G0 is reversible and can be forced to proliferate
Senescent G0 is irreversible and will not go back into cycle
*depends on the cell type

Question 6

Hayflick-phenomenon

Answer 6

After 40~60 mitosis, the cell division is forced to stop (senescence) and Telomerase induces to proliferate again by extending telomere in embryo and cancerous cell

Question 7

4 options for the cell to take in life

Answer 7

1. Proliferation
2. Differentiation
3. Apoptosis
4. Remain undifferentiated
   These stages are balanced in healthy human cell

Question 8

Cdk-cyclin pairs in different phases

Answer 8

Kinase Cyclin
G1 Cdk4,6. D
G1/S Cdk 2. E
S Cdk 2. A(SPF)
G2/M,M Cdk 1(cdc2) B(MPF; M Phase promoting Factor)
All Cdk 7. H(CAK; Cdk Activating Kinase)

Question 9

Determinants of Cdk activity

Answer 9

1. Activating cofactor of cyclin
2. CKI (Cdk Inhibitor prot)
3. Activating phosphorylation (by CAK; Cdk7+cyclin H) on Thr
4. Inhibitory phosphorylations (e.g. by Wee1) on Thr, Tyr
   * inhibition is alwasy dominant

Question 10

Cycle independent function of CAK in G0 phase

Answer 10

subunit of TFIIH

Question 11

Highly conserved phosphatase which mediates deposphorylation the Tyr site phosphrylated by Wee1(Protein Tyr kinase)

Answer 11

Cdc25

Question 12

what happen to the yeast cell if Cdc25 is hyperactive and Wee1 deficient

Answer 12

Due to hyperactive Cdk1-cyclinB, G2 gets too short and starts mitosis earlier. This results to smaller cell than normal
*It’s possible that No Cdk-cyclin complex controlling G2 phase

Question 13

Two CKI family and the significance of it and how to function

Answer 13

CIP/KIP can interupt all phase and INK4 only deal with the G1 phase cyclin-cdk complex.
As binding CKI, cyclin-cdk complex occurs rearrangement in the Cdk active site which renders inactive.

Question 14

Specific CKI which intervenes when DNA damage ocur

Answer 14

p21(CIP/WAF1) a.k.a. Cyclin dependent Kinase Inhibitor 1

Question 15

Main steps of the cell cycle and conclusion with respect to cyclin, cdk, CKI, transcription factor

Answer 15

1. Growth factor (Mitogen) binding to RTK
2. MAPK, Akt/PKB cascase
3. Reprogramming of gene transcription
4. Cyclin D, Cdk4,6 , E2F increase, CKI(INK4) decrease
   * it’s called mitogenic effect of GF

Question 16

After overcome restriction point through Cdk4,6-cyclin D complex, Cdk4,6 and Cdk2 activates which factor?

Answer 16

They activate E2F by phosphorylation of pRB(RetinoBlastoma prot.) and pRB detaches from E2F and starts transcription for genes for S phase

Question 17

Genes under the control of E2F

Answer 17

1. ORC (Origin Recognition Complex) subunit
2. MCM 2~7 (helicase complex)
3. Cdc6, cdt1 (managing the assembly and binding of MCM complex)
4. DNA polymerase alpha
5. PCNA (Proliferating Cell Nuclear Antigen) which is sliding clamp for DNA pol delta/epsilon
6. proteins for further progress of the cycle (e.g. cdc25)
7. TF (e.g. E2F)

Question 18

Mechanism to enter S phase

Answer 18

Increased conc. Of Cdk2-Cyclin E complex phosphorylates CKI(p27) so that it is ubiquitinated from Cdk2-Cyclin A(SPF) then this activates pre-replication complex via phosphorylating MCM2~7, Cdc6, cdt1 to form and activate the helicase.

Question 19

Meaning of Reprogramming transcription

Answer 19

Phenomenon of global change in gene expression that are typically initiated by transcriptional factors

Question 20

Description the process from pre-replication complex to DNA replication

Answer 20

1. From pre-replication complex (MCM2~7, ORC with cdc6, cdt1), SPF phosphorylate MCM2~7, cdc6, cdt1 and activate the complex.
2. After ORC complex with cdc6, cdt1 is replaced by helicase activator and SSBP, DNA is unwinded
3. DNA pol. Alpha, primase, dNTP and NTPs are added and DNA replication occurs

Question 21

cdc25 and Wee 1 different identity and thier functional meachanism

Answer 21

cdc25 is phosphatase which will be active when it’s phophorylated
Wee 1 is kinase which will be active when it’s dephosphorylated
Both of them are turned off and on by PP which is inhibited by active CDK
(Drawing)