Brazeau - Cell Cycle

Question 1

Aneuploidy

Answer 1

Abnormal number of chromosomes Can cause over or under production of genes

Question 2

Four phases of cell cycle

Answer 2

G1 S G2 M Interphase between M phases

Question 3

Growth Phases? Replication of the DNA? Segregation of the DNA

Answer 3

G1 / G2 S Phase M Phase

Question 4

What is the largest segment of the cell cycle?

Answer 4

G1 Phase

Question 5

What is the exception to the G1 phase?

Answer 5

Early cell divisions of embryos proceed w/out G1/G2 phase

Question 6

G2 Phase

Answer 6

Second growth phase, preparation for mitosis

Question 7

What is main regulator of DNA replication? What prevents re-initiation of replication?

Answer 7

MCM helicase kinase activity during late G1/S

Question 8

What controls entry into the cell cycle?

Answer 8

Availability of growth factors

Question 9

What links cell division to conditions in the cell’s environment?

Answer 9

Growth factors

These will initiate cell division

Question 10

Signaling Cascades

Answer 10

Downstream mediators of growth factors

Question 11

Cyclins

Answer 11

Regulate activity of cyclin dependent kinases

Question 12

Cyclin Dependent Kinases (CdK)

Answer 12

Activate components of pathways responsible for DNA synthesis and events of mitosis

Question 13

Cdk Inhibitors

Answer 13

Provide additional control in specific situations

e.g Absence of growth signals or DNA damage

Question 14

Checkpoints

Answer 14

Additional regulation, “quality assurance”

Question 15

What compound regulates the transition from G2 to M?

Answer 15

MPF (CycB / Cdk 1)

Question 16

What binds to cyclins dependent kinases to regulate their activity?

Answer 16

Cyclins

Question 17

MPF

Answer 17

Mitosis Promoting Factor

Cyclin B / CDK 1

Regulates G2 - M

Question 18

What occurs following Cyclin B binding to Cdk1 (forming MPF complex)?

Answer 18

• CDK Activating Kinase (CAK) Adds +P to CDK1
• Wee1 Kinase Adds Inhibitory +P to CDK1
• Cdc25 removes inhibitory-P

- Active MPF initiates M phase

- APC ubiquitinates and targets for proteosomes

Question 19

CAK

Answer 19

Activating kinase, phosphorylates Cdk1 for activation

Question 20

Wee1 Kinase

Answer 20

Adds inhibitory phosphate to Cdk1

Question 21

Cdc25 Phosphatase

Answer 21

Removes inhibitory phosphate added by Wee1 Kinase

Question 22

What tags Cyclin B for degradation?

Answer 22

APC ubiquitinates

Question 23

CdK/Cyclin: Early G1 - R

Answer 23

Cdk 4,6/CycD

Question 24

CdK/Cyclin: G1 - S

Answer 24

Cdk2/CycE

Question 25

CdK/Cyclin: G2 - M

Answer 25

Cdk1/CycB

Question 26

What major complexes regulate Cdks?

Answer 26

Cyclin CAK (activate) Wee1 (inhibit) Cdc25 (activate) CKI (inhibit)

Question 27

Ink 4 Family

Answer 27

Cdk 4,6 Inhibitor Inhibits progression through G1

Question 28

Cip/Kip

Answer 28

Cdk2/CycE (or A) inhibitor Blocks progress through G1 and S **Often involved in cancer**

Question 29

What does growth factor binding to its receptor trigger? What happens if GF removed before R? After?

Answer 29

Synthesis of Cyclin D (need to build this up) Cell will enter G0 Cell cycle will be completed

Question 30

Major growth factors for Cyc D synthesis?

Answer 30

Ras/Raf MEK/ERK

Question 31

What drives the cell cycle through the R-point in G1?

Answer 31

Cdk4,6/Cycd

Question 32

What are main targets of Cdk4,6/CycD?

Answer 32

Retinoblastoma Protein (**Rb**)

Question 33

When **not** phosphorylated, is the role of Rb? When phosphorylated? What kinase phosphorylates the complex?

Answer 33

Binds **E2F**, and **represses transcription genes** for cell cycle progression ## Footnote **Rb dissociates from E2F; transcription proceeds** **Cdk4,6/CycD**

Question 34

What does passage through R and initiation of DNA synthesis require? What inhibits this until the proper time? How is this inhibition removed? What occurs once this inhibition is removed?

Answer 34

Activation of Cdk2/CycE **KIP family (p27)** CycE synthesis increases, p27 decreases DNA synthesis begins

Question 35

DNA Damage Checkpoints

Answer 35

Protect cell from replication errors or pasisng down damaged DNA

Question 36

Spindle Assembly Checkpoint

Answer 36

Ensure chromoosmes are aligned properly so each daughter cell receives one copy of each chromosome

Question 37

How many DNA damage checkpoints are there? How many spindle assembly checkpoints are there?

Answer 37

3x G1 S G2 1x M

Question 38

ATM/ATR

Answer 38

Kinases part of **damage recognition complexes;** phosphorylate downstreak kinases-- ## Footnote **Chk1 / Chk2**

Question 39

Chk1/Chk2

Answer 39

Downstream kinases which phosphorylate **Cdc25; blocking Cdk1 and Cdk2**

Question 40

What phosphorylates p53?

Answer 40

**ATM/Chk2**

Question 41

p53

Answer 41

Transcription factor that regulates trasncription of **CKI 21;** increases lead to increas in p21. p21 inhibits Cdk2/CycE complex, causing G1 arrest