17. System Biology Based Interpretation Of Cell Cycle Regulation

Question 1

How does the DNA integrity is being checked continuously

Answer 1

Via checking DNA damage-> Arrest cecll cycle immediately (G1/S, S, M) by inhibition of Cdk-cyclin complex formation -> Try Repair DNA -> if it’s succesful, cycle continues, otherwise cell must die

Question 2

Negative control elements of the Cell cycle (via diagram)

Answer 2

CHK1,2 inhibits cdc25, which stimulate the G1/S, G2/M(MPF) formation
p15/p16 INK4 inhibits cdk4,6-cyclin D (only G1)
p27 KIP1, p21 WAF1 inhibits all transition (all transition; G1,G1/S, S, G2/M,M)
p53 stimulates p21 WAF1

Question 3

CHK1 and CHK2 roles

Answer 3

ATR(nt excision repair or ongoling replication) on ssDNA phosphorylated CHK1
ATM(disassembly chromatin, dsDNA break) phosphorylateted CHK2
*‘check out from ATM’
After activation of CHK1/2, they phosphorylate cdc25 (deactive) and it is degraded by proteasome.
‘Phosphatase 는 부족한 놈이라 P를 떼어내는게 본능’

Question 4

Overview of cell cycle control

Answer 4

• In 4 phases (interphase, mitosis), the cycles are controlled by cdk and their cofactor cyclin proteins.
• The cdks and cyclins are regulated through protein phosphorylation, dephosphorylation, degradation.
• Exogenous mitogenic stimulation is convincing enough till the cell passes the point of commitment(restriction point) in G1. The cell can either continue dividing or die.
• Cycle can be arrested at the checkpoints at G1/S, S, G2/M depending on DNA integrity, completion of replication, cell size, or kinetochore-microtubule attachment.

Question 5

Cell cycle transition bistable switch (drawing);

Answer 5

1. pRB/Rb in G1/S transition; Cdk2-cyclin E with cdk4,6-cyclin D degrades pRB(Retinoblastoma protein) to make free and active E2F w/ DP(Dimerizing partner)
2. CKI, Wee1, APC in G2/M transition
   * double negative feedback: Wee1, CKI, pRB