Cell Cycle, Apoptosis, and Cancer

Question 1

What are the stages of the cell cycle?

Answer 1

G1/G0->S->G2->M

Question 2

What is done during G1/G0?

Answer 2

G1: RNA and protein synthesis/ cell growth
G0: Cells withdrawn from cell cycle, defective cells

Question 3

What happens during S phase?

Answer 3

DNA is synthesized and replicated to form homologs (2 chromosomes)

Question 4

What happens during M phase?

Answer 4

Mitosis occurs: (prophase, metaphas, anaphase, telophase) nuclear division at the beginning and cell division (cytokinesis) at the end

Question 5

What occurs during G2?

Answer 5

DNA stability is checked

Question 6

What is interphase?

Answer 6

G1, S, and G2

Question 7

What are restiction points and checkpoints and where are they located for the cell cycle?

Answer 7

They are a discrete timepoint where ‘errors’ are checked.
Restriction: before S phase
Checkp: After restriction before S, end of G2, beginning of Metaphase

Question 8

What is the main job of restriction point before S?

Answer 8

If growth factors of cell are limited, restriction occurs and removed cell from cycle

Question 9

What occurs at G1 checkpoint before S?

Answer 9

If there is DNA damage, pulls cell from cycle and trys to fix or goes to trash

Question 10

What occurs at G2 checkpoint before M?

Answer 10

G2 verifies complete genomic duplication, if errors cell is pulled from cycle

Question 11

What occurs at metaphase checkpoint during M?

Answer 11

This checkpoint ensures chromosomes are attached to the mitotic spindle

Question 12

What does cyclin (protein) and cyclin dependent kinases do in cell proliferation?

Answer 12

Activated by many things, they phosphorylate retinoblastoma (Rb) which releases E2F, which is needed to enter S phase from G1.

Question 13

What are cyclin E and A needed for?

Answer 13

E: so that cell cycle can transition from G1 to S phase
A: so that S phase can occur

Question 14

Why is cyclin important to CDKs and what are their main role?

Answer 14

CDK without cyclin are inactive, with cyclin binded, CDKinase is activated to phosporylate substrates so cell cycle can continue/not

Question 15

What is required for full activation of cyclin/CDK?

Answer 15

CDK-activating kinase (CAK!) (phosphorylates)

Question 16

How is cyclin/cdk inhibited?

Answer 16

p27 and WEE1 inhibit, or cyclin cut off by proteasomes

Question 17

Where can Cyclin D-CDK4 and cyclin D- CDK6 be found?

Answer 17

They are found in G1 and help pass cells through the restiction point

Question 18

How does p27 inhibit cyclin/cdk

Answer 18

Binds to both and inactivates

Question 19

How does WEE1 inhibit cyclin/cdk?

Answer 19

WEE1 inhibits by adding another phosphate to the (roof site) and inactives cdk.

Question 20

how is WEE1 phosphorylation reversed?

Answer 20

CDC25 phosphotase

Question 21

How is Cyclin S and M activity downregulated to move into anaphase?

Answer 21

APC (anaphase promoting complex, cyclosome), member of ubiquitin fam, is activated, ubiquinating S and M, which signals for destruction by proteosomes, CDK inactivated, moves cells to anaphase

Question 22

What is p53, what activates it, and what does it activate?

Answer 22

p53 is the guardian of the genome, a trasncription factor.

It is activated by protein kinases (which is activated by DNA damage), and is regulated by MDM2

It activates transcription gene of p21

Question 23

How is p21 important to the cell cycle?

Answer 23

binds to cyclin cdk to inactivate, inactivating G1 and S phase, keeping Rb active, and E2F sequestered to it

Question 24

What is the extrinsic pathway for apoptosis?

Answer 24

Ligand binds to death receptor (FAS or TNFalpha), activates procaspase8 to active caspase-8, activates Caspases 3,6&7, APOPtosis

Question 25

What is the intrinsic pathway for apoptosis?

Answer 25

DNA damage activates p53 & BAX/BAK, BAX makes ports which causes mito cyto C to leak out and bind APAF-1, forming Apoptosome, which activates caspase 9, activating caspases 3,6,7 and apoptosis

Question 26

What is BCL2 and BAX? What happens if cancer gets a hold of these?

Answer 26

BCL2 inhibits apoptosis, BAX activates apoptosis. If cancer is active, will upregulated BCL2 and downregulate BAX so cancer cells survive!

Question 27

What is a oncogene?

Answer 27

a gene that normally promotes cell cycle

Question 28

What is a tumor suppressor gene and what does it do?

Answer 28

a gene that inhibits cell cycle, promotes apoptosis, couple DNA damage to cell cycle

Question 29

what happens if a protooncogene is mutated by point mutation, deletion or translocation?

Answer 29

Known as "Gain of function" become oncogene which increases expression

Question 30

What is an example of an oncogene, and its mutation?

Answer 30

HER2 receptor, a point mutation changes valine to glutamine= NEU. which allows kinase to remain active even when to ligand. results in breast cancer (Ras)

Question 31

Example of a tumor suppressor gene, and mutation?

Answer 31

Rb, because binds E2F to stop cell division. can cause cararacts when mutated and gets 'second hit'

Question 32

What do metastasis supressors do, example?

Answer 32

Cell adhesion proteins 1. prevent tumor cells from dispersing 2. block loss of contact inhibition 3. inhibit tumor metastasis

Question 33

What are the steps/mutations that lead to metastasized cancer?

Answer 33

Loss of APC, Mutation in Ras to always be on (oncogene), loss of tumor suppressor, loss of p53 activity, metastasis :(

Question 34

What are the 6 hallmarks of cancer?

Answer 34

1. Ability to grow alone (HER2) 2. Tumor suppressor failure 3. Invading and metastasis 4. Telomerase up activation 5. Angiogenesis 6. Resisting cell death from apoptosis (mutated BAX)

Question 35

Describe viral oncogene to transformed cell

Answer 35

Protooncogene, infected by virus, attacks and hijacks cell, Virus replicates and protooncogene turns into oncogene. infects normal cell, turning to tumor cell

Question 36

HPV mechanics?

Answer 36

E6 binds p53(loss of t sup.) , E7 binds Rb (releases E2F), activates cell cylce/proliferation

Question 37

What do alkylating agents do compared to antimetabolites?

Answer 37

Alkylating block DNA replication | Antimetabolites inhibits S phase

Question 38

What do cytotoxic antibiotics do compared to mitotic inhibitors?

Answer 38

Cytotoxic intercalate between DNA bases to inhibit S/G2 phase Mitotic arrest cells in mitosis during metaphase

Question 39

What do Topo I inhibitors do compared to Topo II?

Answer 39

Topo I inhibitors result in tangled DNA=S phase | Topo II inhibitors result in tangled DNA in G2 phase