Exam 3 - Cell Cycle I

Question 1

What is the importance of erythrocyte biology?

Answer 1

To make blood

Question 2

What is cancer?

Answer 2

A disease of excess cell proliferation

(Cell divides uncontrollably)

Question 3

What is the basic cell cycle?

Answer 3

• moment cell is born to the moment it is the the mother of 2 cells

1 cell growth and chromosome replication

2. chromosome segregation
3. cell division

Question 4

What is the cell cycle control system?

Answer 4

A cells’s complex network of regulatory proteins. THat govern the cell cycle that is essentially a series of bipchemical switches. These proteins make sure the events in the cycle occur at appropiate time and also work in response to outside and inside signals.

duplication of cells contents like organelles is also an aspect of cell cycle growth

Question 5

What are the major chromsomal events in the cell cycle?

Answer 5

1. chromosome duplication
   
   1. in the s phase of cell cycle (DNA synthesis phase)
2. Chromosome segregation
   
   1. occurs in the M phase of cell cycle
3. Cytokinesis
   
   1. cell division
   2. occurs in the M phase

Question 6

What are the stages of eukaryotic cell division?

Answer 6

1. Prophase
   
   1. chromosomes condense into rigid rods called sister chromatides (become attached to mitotic spindle: a bupolar array of microtubles)
2. Metaphase
   
   1. sister chromatids line up at equator of cell attached to opposite poles of spindle
3. Anaphase
   
   1. sister chromatids become daughter chromosomes are pulled to opposite poles of spindle
4. Telophase
   
   1. Spindle disassembles, chromosomes packaged into separate nuclei, cytokinesis occurs

Question 7

What are the four phasees of the Cell Cycle?

Answer 7

• G1, S, G2, M
• G1 phase
  
  • Gap phases to allow more time for growth
• S phase
  
  • Synthesis of DNA
• G2 phase
  
  • Gap phases to allow more time for growth
• M phase
  
  • seperate chromosomes and divide cells

Interphase is G1, S and G2

Question 8

What are the check points of the cell cycle control system?

Answer 8

1. check point 1
   
   1. G1 to S
   2. START - cell commits to cell cycle entry and chromosome duplication - (restruction point)
2. check point 2
   
   1. G2/M
   2. If DNA is duplicated
3. check point 3
   
   1. M phase
      
      1. Metaphase to anaphase
   2. transition - trigger sister chromatid separation and cytokinesis

Question 9

What are example model organisms for studying the cell cycle?

Answer 9

• Yeast (single cell fungi)
  
  • Helped us learn about cell cycle
  • bud first appeats at g1
  • genes identified in yeast enode CDC of cell division cycle genes
• Animal embroyos
  
  • frog embroyos s phase and M phases are 15 minutes each and not detectable G1 or G2 phase
  • fibrobalsts are a mammalian cell line that cen be used to study cell cycle but they have a FINATE amount of divisions
  • Immortalized cell lines grow forever

Question 10

What are cyclins?

Answer 10

• protein that regulate cdks
  
  • expression controls what step the cell is in
• cyclin levels varies throughout the cell cycle
• cdks are dependsent on cyclins and must be ount to cyclin to have protein kinase activity (w.o it cdk is inactive)
  
  • cdk complexes trigger cell cycle events
• four classes
  
  1. G1/S cyclins
     
     1. start cycle
  2. S cyclins
     
     1. duplicate DNA
  3. M cyclins
     
     1. Mitosis
  4. G1 cyclins
     
     1. govern activity of G1/S cyclins

Question 11

What are cdks?

Answer 11

• Cyclin dependent kinase
• Activates of CDKs rise and fall during the cell cycle but NOT CONCENTRATION
  
  • Concentration of CDK stays constant
• Causes cyclical changes in phopshorlaytion of substrates (proteins ) downstream to activate them and regulate cell cycle events
• cell cycle is governed by CDKs

Question 12

What are the four classes of Cyclins?

Answer 12

1. g1/s cyclins
   
   1. start the cell cycle
   2. activates cdks in late g1
   3. helps trigger progrssion and commitment cell to the cycle
   4. levels drop in S
2. S cyclin
   
   1. duplicate DNA
   2. binds CDKS after progression through start
   3. helps stimulate chromosome duplication
   4. s cyclin levels remain high until mitosis
3. M cyclins
   
   1. Activate Cdks that stimulate entry into mitosis at g2/M checkpoint
   2. M cyclins removed at mid mitosis
4. g1 cyclins
   
   1. govern activity of g1/s cyclins through (control progression through start checkpoint)

Question 13

What is CAK?

Answer 13

CAK is Cdk activating kinase

when cyclin is bound to CDK, the active site on CDK is open ( T loop is moved out of active site which is partial activation) . CAK then phosphorlaytes CDK at the T loop (cave site) which = Full activation

Question 14

How does Wee1 kInase and cdc 25 work?

Answer 14

Wee1 kinase inhibits cdk activity by phosphorylating the roof “site”

Cdc25 is a phosphatase that dephosphorylates the roof site to increase cdk activity

Question 15

What CKI proteins?

Answer 15

• inhibits the cyclin-cdk complex
• binds to both to inactivate
• primarily used for control of g1/s-cdks and S cdks early in cycle

Question 16

how does CKI relate to diease?

Answer 16

• familial heredotary melanoma
• Mutation in INK4A
  
  • INK4A is a CKI involved in the g1 phase of the cell cycle
• Cannot control cell cycle and cells grow uncontrollably and you get cancer (melanoma)

__________________________________

• Cancer causing in a different gene
  
  • p53 is a major tumor suppressor and influences many genes
  • causes upregualtion of p21 which is a CKI to stop cell dvisions
  • when p53 fails it causes lower p21 expression and cells will divide uncontrollably

___________________________________

Question 17

What is SCF

Answer 17

• SCF (Ubiquitin ligase)
• • adds ubiquitin to CKIs
• remember ubiquitination stimualtes destruction of proteins
• SCF adds ubiquitin to phosphotyalted CKI and depends on F-box subunit to recongize its target protein
• occurs in g1
• restores activity of activity of S-CDK complex

Question 18

How does MCdk and wee1/cdc 25 relate?

Answer 18

• activation of primed M-Cdk is by Cdc25 removes inhibitory phosphates from M-cdks
• activation of M-cdk complex for mitosis

Double Circuit Positive feedback
* Positive feedback:
* activation of M-Cdk complex will activate Cdc25 phosphatase to remove phosphate from roof site - release inhibition
* also wee1 kinase is inhibited so that roof site is not phosphorylated
*

Question 19

how does the progression from metaphase to anaphase in cell cycle

Answer 19

• NOT REGULATED BY PROTEIN PHOSPHORYLATION but REGULATED BY PROTEIN DESTRUCTIONS
• APC/C : anapase-promoting complex (or cyclosome)
• APC/ C is a ubiquitin ligase
  
  • catalyzes addition of Ubiquitin to proteins to cause destruction
  • 2 major proteins affected in this system
    
    • cohesin + securin
    • Cohesin (structural maintenance chromasomal proteins)
      
      • sister chromatids are glued together clong their length by this protein
    • Securin
      
      • protects cohesin protein linkages that hold sister chromatids pairs together in early mitosis by inhibiting a protein called separase (an enzyme that cleaves cohesin)

Question 20

What is separase?

Answer 20

undoes the glue (cohesion) holding chromatids together

Necessary for sister chromatids to become chromsomes

Question 21

Question 22

when does the destruction of inhibitor securin by APC/C occur?

Answer 22

at metaphase to anaphase transisiton

indrecertly activates protease called separse that separties sisterchromatids and anaphase begins

Question 23

How does Mitosis and APC/C relate and what are the steps?

Answer 23

• APC/C are targeting S cyclins and M cyclins
• inactivated by binding of Cdc25
• leads to addition of polyubiquitin to M cyclin in M-cdk complex
• Cyclins are destroyed and cdk dephosphorylated
• to prevent more DNA and chromosomes synthesis S and M cyclin are removed .

1. APC/C levels rise in mid-mitosis
2. APC/C adds ubiquitin on targets to destroy proteins
3. APC/C
4. Destruction of Securin (inhibitor of Separase)
5. Separase (protease)
6. Cleaves cohesin sister chromatids come apart
7. APC/C levels rise in mid-mitosis
8. APC/C adds ubiquitin on targets to destroy
9. APC/C destroys cyclins of Cdk-cyclin complexes
10. No cyclins and no complexes left