Cell Cycle

Question 1

G0

Answer 1

• Quiescent, intact proliferation capacity, non-cycling

Question 2

G1 and Regulation

Answer 2

• Duration between completion of cell division and initiation of DNA replication where cells start building cell mass
• Cyclins: C,D 1-3, E 1-2, F, G
• CDK4/CDK6 binds with D

Question 3

S and regulation

Answer 3

DNA replication

• Cyclin A binds with CDK2 and CDK1

Question 4

G2 and regulation

Answer 4

Duration between completion of DNA replication and initiation of cell division
• Cyclins B 1-2 binds with CDK1

Question 5

M-phase

Answer 5

Mitosis

Question 6

(1) Kinase: CDK1, Cyclin A

Answer 6

• Triggers G2 to M transition

* Cyclin A is synthesized in S and destroyed starting at prometaphase

Question 7

(2) Kinase: CDK1, Cyclin B

Answer 7

• Phosphorylation of the retinoblastoma susceptibility protein in G1
• Triggers passage of the restriction point and cyclin E synthesis in some cell types

Question 8

(3) Kinase: CDK4/6 cyclin D

Answer 8

• Phosphorylation of the retinoblastoma susceptibility protein in G1
• Triggers passage of the restriction point and cyclin E synthesis in some cell types

Question 9

(1) INK4 family (p16,15,18,19) (Cyclin D)

Answer 9

• Twisting of the Cdk upper lobe blocks cyclin binding or interferes with ATP hydrolysis
• Cooperates with the retinoblastoma susceptibility protein in growth regulation
• Cell-cycle arrest in senescence
• Altered in a high percentage of human cancers

Question 10

(2) Cip/Kip families (p21-Cip1, p27-Kip1, p57-Kip2) (Cyclin A and B)

Answer 10

• A loop insinuates into the upper lobe of the Cdk and blocks ATP binding
• P21
(i) Induced by p53 tumor suppressor
(ii) Cell-cycle arrest after DNA damage
(iii) Binds PCNA and inhibits DNA synthesis
P27
-cell cycle arrest in response to growth suppressors like TGF-Beta and contact inhibition

Question 11

What is the restriction point?

Answer 11

E-CDK2 complexes drive pRB hyperphosphorylation, this liberates E2F transcription factors from pRb control, enabling the E2Fs to trigger increased transcription of the cyclin E and E2F1

Question 12

Cancer initiation

Answer 12

• Simple mutation in one or more genes that control key regulatory pathways of the cell
• Change in DNA sequence
• Irreversible

Question 13

Cancer Promotion

Answer 13

• Selective functional enhancement of signal transduction pathways that were induced by initiator by continuous exposure
• Epigenetic event
• Over long period of time
• Reversible in early stages

Question 14

Cancer progression

Answer 14

• Continuing change of the basically unstable karyotype
• Further changes in karyotype
• Irreversible changes
• Conversion of benign tumors into malignant neoplasms

Question 15

Tumor suppressor genes

Answer 15

(6) Ex: p53, Rb, p14ARF, P16INK4A (gene mutation, deletion, CpG island methylation in promoter)

Question 16

Radiation therapy

Answer 16

• Effective on cells which have

(i) Reproductive activity
(ii) Cells which no longer have dividing future ahead
(iii) Cells with morphology and function are least fixed
(iv) Direct deposit of energy to break DNA bonds
(v) Hydrolysis of water to produce powerful damaging free radicals

Question 17

Chemotherapy

Answer 17

•	Alkylating agents 
(i)	Crosslinking of DNA chains
•	Antitumor antibiotics
(i)	Inhibition of topoisomerase II
(ii)	Intercalation
•	Antimetabolites
(i)	Inhibition of enzymes 
(ii)	Introduction of false substances in DNA “poisons of the division spindle” 
•	Enzymes	
(i)	L-Asparaginase
(ii)	Enzymatic cleavage of asparagine 
•	Unclassified chemotherapeutics
(i)	Crosslinking of DNA chains, destruction of enzymes

Question 18

Apoptotic initiators

Answer 18

caspases 8,9,10

Question 19

Apoptotic executioners

Answer 19

capases3,6,7

Question 20

Anti-apoptotic

Answer 20

BCL-2 family

Question 21

Pro-apoptotic

Answer 21

BH3 and BAX family

Question 22

Autophagy

Answer 22

(a) Self destruction
(b) Due to starvation
(c) Membrane blebbing, accumulation of two-membrane autophagic vacuoles
(d) Caspase independent and increased lysosomal activity

Question 23

• Mitotic catastrophe

Answer 23

(a) Aberrant mitosis
(b) Associated with deficiencies in cell cycle checkpoints, formation of giant cell, micronuclearization and multinucleation
(c) Defects in cell cycle checkpoints
(i) P53- G2 checkpoint
(ii) BUBR- spindle checkpoint
(iii) APC- spindle assembly
(d) Hyper amplification of centrosomes
(i) Usually in subsequent cell cycle
(e) Capspase-2 activation during metaphase
(i) Delayed apoptosis