HRR: cell cycle

Question 1

what occurs in each step of interphase, generally

Answer 1

G1: metabolically active cells
S: DNA synthesis
G2: cell growth and preparation

Question 2

what is G0?

Answer 2

Cells can exit G1 and enter G0, where they sit and wait to re-enter the cycle. They can re-enter in response to stimuli.

Question 3

In what phase of the cell cycle do we find each cyclin

Answer 3

G1: D
S: E
G2: A
M: B

Question 4

What are Cyclin-Dependent Kinases (CDK)

Answer 4

Enzymes that phosphorylate a large range of protein substrates (cyclins) required to complete the cell cycle. they bind cyclins to form active CDK/cyclin complexes. Their levels remain pretty constant during the cell cycle.

Question 5

which cyclins and CDKs bind in G1

Answer 5

CDK4 or CDK6 and cyclin D

Question 6

which cyclins and CDKs bind in the G1 to S transition

Answer 6

CDK2/cyclin E

Question 7

which cyclins and CDKs bind in the S phase

Answer 7

CDK2/cyclin A

Question 8

in S to G2 transition, which cyclins and CDKs bind

Answer 8

CDK1/cyclin A

Question 9

in G2 to M transition, which cyclins and CDKs bind

Answer 9

CDK1/cyclin B

Question 10

Describe maturation Promoting Factor (MPF)

Answer 10

It is the CDK1/cyclin B complex. It is a master regulator of the G2 to M transition, and it functions via phosphorylating proteins involved in mitotic processes

Question 11

What are the major outcomes of maturation promoting factor

Answer 11

• Chromatin condensation
• Breakdown of nuclear envelope
• Formation of mitotic spindle

Question 12

How do cyclins regulate CDK activity

Answer 12

Via fluctuation of the amount available; changes in its synthesis and degradation impact the amount of cyclin available to bind to CDK, regulating its action

Question 13

Describe reversible phosphorylation of CDK/Cyclin Complexes

Answer 13

while cyclin binding CDK forms an active complex, sometimes phosphorylation is required. phosphorylation can further activate (CDK activating kinase) or inactivate (CDK inhibitory kinase) the complex, depending on where phosphorylation occurs.

Question 14

Describe Cdc25 phosphatases

Answer 14

Cdc25 phosphatases activate the CDK/cyclin complex via dephosphorylation of the alternate sites

Question 15

What are Cyclin-Dependent Kinase Inhibitors (CKI)

Answer 15

They bind to CDK/cyclin complexes and inhibit their activity. Growth factors regulate their levels.

Question 16

what are the two big examples of CKI’s

Answer 16

p16 and p21

Question 17

what does p16 do?

Answer 17

tumor suppressor gene that is a member of INK family that inhibits CDK4/cyclin D and CDK6/cyclin D and results in G1 arrest. Loss of this function enables the complexes to remain active

Question 18

what does p21 do?

Answer 18

tumor suppressor gene that is part of the cip/kip family and inhibits CDK2/cyclin E and blocks G1 to S.

Question 19

What is the G1 Restriction Point

Answer 19

A decision point that occurs in late G1; if a cell passes through this it is committed to S phase entry and completion of the cell cycle

Question 20

What is Growth Factor Control

Answer 20

The presence of growth factors stimulates progression through G1 restriction point, while the absence of growth factors stops the cells at the restriction point, and they may enter G0

Question 21

What in an example of a receptor activated by growth factors in the G1 checkpoint?

Answer 21

The EGF receptor (tyrosine kinase that initiates Ras-MEK-MAP kinase pathway)

Question 22

Describe the EGF receptor in the context of the cell cycle

Answer 22

• Cyclin D is expressed
• Cyclin D binds CDK4 and CDK6, forming CDK/cyclin complexes
• Rb protein is phosphorylated by the complex and causes it to dissociate from E2F family of transcription factors
• E2F moves to nucleus and activates transcription of target genes required for cell cycle progression through G1 to S

Question 23

E2F activates transcription of…

Answer 23

Cyclin E, cyclin A, DNA polymerase proteins

Question 24

What are gain of function mutations

Answer 24

They result in a loss of cell cycle control due to unregulated progression through the G1 restriction point; often a product of oncogenes

Question 25

What are the DNA Damage Control Checkpoints

Answer 25

They can arrest the cell cycle progression in response to DNA damage or unreplicated DNA; it is not the same as a restriction point

Question 26

What is ATR

Answer 26

Kinase that is activated by single strand breaks, UV damage, or unreplicated DNA; phosphorylates CHK1, which phosphorylates cdc25 and prevents it from activating the CDK/cyclin complexes. This leads to inactivation of cyclins in the S phase and arrest of the cell cycle

Question 27

What is ATM

Answer 27

Kinase activated by double strand breaks; phosphorylates CHK2, which phosphorylates cdc25 and inactivates it. This leads to inactivation of cyclins in the S phase and arrest of the cell cycle

Question 28

Describe the role of Tumor Suppressor Genes

Answer 28

They encode proteins that function by regulating the cell cycle in response to things like DNA damage. Mutations to both copies of these genes can cause cellular transformation and lead to tumor development

Question 29

What does tumor suppressor gene Rb do

Answer 29

Binds E2F and inhibits transcription of target genes; results in G1 arrest. this occurs when Rb is not phosphorylated

Question 30

What does tumor suppressor gene p53 do?

Answer 30

the daddy of all tumor suppressor genes. ATM phosphorylates p53, which then produced p21. p21 will inhibit CDK2/cyclin E complex formation. this complex being blocks prevents phosphorylation of Rb, which effectively prevents G1 to S transition