Exam #4 Cell Cycle Flashcards Preview

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Flashcards in Exam #4 Cell Cycle Deck (41):
1

Four Stages of the Cell Cycle

- M= Mitosis, when the cell dividies
- G1= Growth period the precedes DNA synthesis
-S= DNA synthesis/replication to form two sister chromatids attached at centromere
-G2= Second period of growth the precedes cell division

2

Stages of the Cell Cycle that Comprise Interphase

Interphase is the time between cell divisions

- G1
- S
- G2

3

Cyclin-CDK Complexes of M-Phase

- Cyclin A/CDK1
- Cyclin B/CDK1

4

Cyclin-CDK Complexes of Mid G1 Phase

- Cyclin D/CDK 4
- Cyclin D/CDK6

5

Cyclin-CDK Complexes of Late G1 Phase

Cyclin E/CDK2

6

Cyclin-CDK Complexes of S Phase

Cyclin A/CDK2

7

Contact Inhibition

- Cell - Cell contact usually inhibits cell division
- This "contact inhibition" is lost in cancer
- Cell - ECM contact does the opposite

8

Growth Factors

- Molecules that stimulate cell growth/division
- PDGF, EGF, nerve growth factor, and insulin-like growth factor 1 are examples

9

Growth Factor Receptors

- Intrinsic Tyrosine Kinase
- Ligand (growth factor) binds to receptor & triggers receptor dimerization & autophosphorylation or tyrosine residues within the receptor
- Phosphotyrosine residues are docking sites for signaling molecules

10

GRB2, Sos, & Ras

- GRB2= adapter protein that binds phosphotyrosine residues
- Sos= Guanine Nucleotide Exchange Factor, activates Ras
- Ras= G-Protein that is activated by SOS

11

Raf, MAP kinase kinase, MAP kinase

- Ras activates the protein kinase Raf
- Raf phosphorylates & activates MAP Kinase Kinase (MEK)
- MAP Kinase Kinase phosphorylates & activates MAP Kinase
- MAP Kinase translocated to the nucleus and stimulates c-Fos transcription
- End result= progression through the restriction point

12

Early Response Genes

- Growth factor added to cell in G0 results in a burst of transcription
- Genes transcribed in this initial phase are "early response genes"
- Includes c-Fos, c-Jun, and c-Myc

13

Delayed Response Genes

- Genes transcribed in response to c-Fos
- Encode more transcription factors & Mid/Late G1 Clycin-CDKs

14

Why is phosphorylation of Rb important?

It stimulates progression through the restriction point and renders the cell cycle growth factor independent

15

What kinases phosphorylate Rb?

- CDK 4 & CDK 6 (Cyclin D regulated) initially
- CDK 2 (Cyclin E regulated) secondarily

16

How is cyclin A-CDK2 inhibited?

p27-KIP1

17

What does cyclin A-CDK2 inhibition prevent?

DNA Replication

18

How is cyclin A-CDK2 inhibition relieved?

Cyclin E/CDK 2 (late G1) phosphorylation of p27-KIP1

19

How is entry into mitosis coupled to completion of DNA replication?

- Cyclin A & B/CDK1 are required for entry into mitosis
- Both phosphorylated and inactive until replication is complete
- Once replication is completed, Phosphatase Cdc25C removes inhibitory phosphate

20

Why would normal cells not divide if chromosomes were not correctly attached to the mitotic spindle?

- Anaphase is delayed until chromosomes attach to the spindle
- Attachment activates the anaphase promoting complex (APC)
- APC allows ubiquitination of cohesin that holds sister chromatids together at the centromere
- Sister chromatids then move apart

21

ATM

- Senses replication forks i.e. ongoing replication
- ATM prevents dephosphorylation & activation of Cyclin A/B- CDK1
- ATM is active as long as replication forks are present; thus entry into M-phase is dependent on completion of replication

22

Checkpoint Kinase

- ATM activated
- Blocks the action of Phosphatase Cdc25C i.e. blocks activation of Cyclin A/B-CDK1 when replication is ongoing

23

p53

- Normally unstable transcription factor
- Stabilized by ATM/ATR of DNA damage checkpoint
- Upregulates p21-CIP1

24

p21-CIP1

- Inhibitor of Cyclin/CDK 1 & 2
- Blocks entry into S & M phase

25

Define Apoptosis

programmed cell death

26

Outline Apoptosis

1) Chromosome & Cytoplasmic condensation
2) Nuclear Fragmentation
3) Cell Fragmentation & Blebbing
4) Apoptotic Bodies formed
5) Phagocytosis

27

Caspases

- Caspase 9= Initiator Caspase
- Caspase 3= Executioner Caspase

28

How does p53 activation lead to an efflux of cytochrome c from the mitochondria?

- One of the targets of p53 is the Bcl-2 family of proteins, including PUMA, BID, & BAX
- BAX activation forms a channel in the mitochondira
- Cytochrome C comes out

29

G0

Cells that have differentiated and are no longer dividing exit the cell cycle and are in "G0"

30

List the checkpoints in the cell cycle

- G1/S
- G2/M
- Metaphase/ Anaphase
- DNA damage checkpoint

31

G1/S Checkpoint

- Start/ Restriction point
- Cell determines if conditions are favorable for division

32

G2/M

Ensures all the DNA has been replicated

33

Metaphase/Anaphase

Chromosomes are evaluated to ensure they are attached to the mitotic spindle

34

DNA Damage Checkpoint

- Occurs continuously throughout the cell cycle
- Cells with damaged DNA arrest and repair
- IF the cell cannot repair, undergoes apoptosis

35

Cyclin-CDK

Cyclin= Regulatory subunit
CDK= Serine/Threonine Kinase

36

What mechanism degrades cyclins so they are only present at a specific point in the cell cycle?

Ubiquitin proteolysis

37

How is CDK activity regulated?

Phosphorylation, Dephosphorylation & CDK Inhibitors

38

c-Fos

Transcription factor that stimulates the transcription of the delayed response genes

39

INK4

- Growth Inhibitory Factors
- Compete with Cyclin D for binding to CDK 4/6
- Inhibit CDK 4/6

40

DNA Damage Checkpoint

- Requires ATM & ATR Kinases
- ATM senses ds-DNA breaks
- ATR senses UV damage & certain drug damage
- Block Phosphatase Cdc25 A & C, and phosphorylate p53

41

Ataxia Telangiectasia

- Rare inherited disorder w/ effects on nervous & immune system
- Ataxia= progressive balance problem
- Telangiectasia= small widened blood vessels in skin
- Mutation of ATM impairs cell response to ds-DNA break
- Highly sensitive to radiation exposure