9-15 Cell Cycle I

Question 1

Name the 4 Phases of the cell cycle

Answer 1

1) M PHASE

INTERPHASE (Continuous Cell Growth) PARTS:

2) G1 phase Go
3) S Phase [DNA replication]
4) G2 phase

Question 2

What is the order of division within the M Phase

Answer 2

1st: Nuclear Division //
2nd: Cytoplasmic Division (Cytokinesis)

Question 3

What are the common cell cycle checkpoints for G2 CheckPoint / Entering ___ PHASE ? [3]

Answer 3

Entering M Phase / G2 checkpoint:
1-Is all DNA replicated
2- DNA damage?? If so= CELL CYCLE ARREST
3-Is environment favorable

Question 4

Common Cell cycle checkpoints for G1 Checkpoint / Entering ____ phase? [2]

2)Why is this checkpoint different from others?

Answer 4

Entering S phase / G1 checkpoint:

A: MOST IMPORTANT CHECKPOINT/SIGNAL=dictates [Divide or Die]
B: Is environment favorable?

2) Different because there is no going back and this is the [Divide or Die] decision checkpoint based on growth of mitogenic factors. +Growth = Divide /S phase

Question 5

Common cell cycle checkpoints for Mitotis Checkpoint / Leaving ____ Phase

Answer 5

Metaphase Checkpoint / Leaving M PHASE

1) Are all chromosomes attached to spindle?
IF NOT = Anaphase WILL NOT proceed in normal cells

Question 6

The Control/Checkpoint system of Cell Cycles ensures what 4 things

Answer 6

1. Proper timing
2. Correct Order
3. Feedback mechanisms
4. Phases only occur ONCE per cell cycle

Question 7

Cdk(___ ___ ___) relies on ___ binding for it to become activated.
2) What are these CdK responsible for?

3) When are these CdK degraded in a cell cycle?
4) When are Cyclins degraded?

Answer 7

CdK(Cyclin-Dependent Kinase) relies on Cyclin[different in each cycle] to bind to it for it to be ACtivated!

2) Cdk turns on different phases of the cell cycle and are different for each phase (like Cyclins)
3) CdK is NOT degraded until the [Go] phase! Otherwise, they stay around for the entire ride!
4) After a cyclin has done its duty, its levels drop down when entering a new phase

Question 8

[T or F] Concentrations of the 3 major CYCLINS does NOT oscillate during the cell cycle.

Answer 8

FALSE! the 3 major CYCLINS have concentrations that DO oscillate during the cell cycle while… Cdk conc. stays constant and ends up exceeding cyclin amount until [Go].

Question 9

In regards to Cyclins and Cdk, war happens in Late G1 / almost S-phase?

Answer 9

[Divide or Die] check point is passed 1st and then rising

G1/S-cyclin levels bind and lead to activation of G1/S-Cdk which triggers progression thru the start checkpoint!

Question 10

In regards to Cdk what actually triggers DNA replication and “some” early mitotic events?

Answer 10

S-Cdk (after being activated by S-cyclins) form at start of S-phase and trigger DNA replication as well as some “early” mitotic events

Question 11

1-When do M-Cdk form?
2-When are M-Cdk activated and what do they do?
—————————————————-
3) What does APC/C do?

Answer 11

1) M-Cdk forms DURING G2 phase but held inactive until the end of it
2) M-Cdk are activated AT THE END OF G2 and officially trigger early events of mitosis.&raquo_space;>M-Cdk is turned off when APC/C starts because APC/C destroys M-cyclins

3: APC/C are separate regulatory proteins that initiate (metaphase—>anaphase) transitions during mitosis!

Question 12

1)What kinase is responsible for inactivating the Cdk-cyclin complex and how does it do this?
B: How could we reverse this inactivation?

2) After cyclin binds to Cdk, how is the [Cdk-cyclin] complex activated as a group?

Answer 12

[Wee1 ] Kinase INACTIVATES Cdk-cyclin by phosphorylating 2 closely spaced sites above the 1st active site.

2) CAK enzyme places FIRST activating phosphate on (Ser/Thr AA residues) of the
[Cdk-cyclin] complex

Question 13

What happens when the Cdc25 ______ is ELEVATED?

Answer 13

Cdc25 PHOSPHATASE removes inhibitory phosphate pair from [Cdk-cyclin] complex–>reactivation. Reactivating too many [Cdk-cyclin] will lead to accelerated cell cycle stimulation
—–>CANCER!

Question 14

What is basically the step-wise process of regulating Cdk and cyclins? [4]

Answer 14

1st-cyclin binds to Cdk to activate Cdk= [Cdk-cyclin]

2nd- CAK enzyme phosphorylates Ser/Thr AA residues on the [Cdk-cyclin] complex–>ACTIVATE [Cdk-cyclin]

3rd- [Wee1 Kinase] adds 2 inhibitory phosphates to 2 close sites above active site–>INACTIVATION

4th- Cdc25 phosphatase removes inhibitory phosphates———>REactivation of [Cdk-cyclin]

Question 15

Describe Full Process of activating M-Cdk

Answer 15

1: As M-cyclin levels rise, M-cyclin binds to Cdk I =
[Cdk-cyclin] complex
2: activating phosphate then placed on [Cdk-Mcyclin] by CAK, followed w/inhibitory phosphate pair placed close to activation site by [Wee1 Kinase]

3: Resulting inactive [Cdk-Mcyclin] complex is then REactivated AT END OF G2 by Cdc25 phosphatase which removes inhibitory phosphate pair
4: now REactivated [Cdk-Mcyclin] is able to inhibit Wee1 Kinase AND is further stimulated by positive feedback from its other activated brothers

Question 16

SCF

Answer 16

Ubiquitin Ligase Complex that promotes DEGRADATION of G1/S cyclin = STOPS CELL CYCLE PROGRESSION

Question 17

1) What is Rb (____ _____)?
2) What is E2F

3)How would you INactivate Rb and what is the result?

Answer 17

1) Rb (Retinol Blastoma) susceptibility factor is a pocket binding protein that binds/inactivates E2F=NO S-PHASE
[Rb/E2F Quiescent]

2) E2F upregulates S-phase genes–> G1/S-cyclin &S-cyclin production
3) When G1-Cdk comes and PHOSphorylate/INactivate Rb, Rb releases E2F –> E2F starts up S-Phase

Question 18

When is Rb phosphorylated/_____[active/INactive]

Answer 18

Rb is PHOSphorylated/INactive during the G1——>S phase transition. (Allows E2F to start up s-phase stuff)

Question 19

When is Rb DePhosphorylated/_____[active/INactive]

Answer 19

Rb is DePhosphorylated/ACTIVE during M—–>G1 phase transition (You don’t want E2F doing crazi S-phase stuff during Mitosis)

Question 20

How do viruses cause upregulation in S-genes?

Answer 20

VP (viral proteins) OUT compete E2F tx factor for its binding pocket in the Rb protein and thus allow E2F to freely roam and overactivate [E2F element S-gene]!—>cell proliferation/CANCER

Question 21

How does p53 assist in preventing cancer? [3]

2) This protein is effectively known as …..

Answer 21

*[G1] Damaged DNA activates protein kinases that phosphorylate p53(this DISbounds it from Mdm2 and activates p53!). —>
**p53 accumulates in high levels and stimulate tx of [CK1/p21/waf1] and also binds to/INactivates
[G1/S Cdk-cyclins] =arresting cell in G1——–>
**This allows time for cell to get it’s act together/prevent cancer

2)p53 = “GUARDIAN OF THE GENOME”

Question 22

Mdm2

2)What is an “alternative” process that occurs to this protein after DNA damage?

Answer 22

Binding Protein that BINDS to UNphosphorylated/INactive p53 and promotes their ubiquitylation/ destruction

2) Alternatively DNA damage also induces either Mdm2 phosphorylation OR decrease Mdm2 production——>will INC p53 levels as a result

Question 23

1) [Ck1/p21/waf1] ?

2) What activates this?

Answer 23

1) Cyclin-Kinase inhibitor with 3 names lol! It STOPS cell cycle from proceeding –>gives cell enough time to repair before moving on after DNA damage in G1
2) [Ck1/p21/waf1] is activated by high levels of activated/phosphorylated p53

Question 24

How does early embryonic cell cycles differ from adult cell cycles?

Answer 24

Many Cell-cycle control/regulating events are MISSING in early Embryonic cell cycles!