Mitosis & Meiosis

Question 1

what are the phases of the cell cycle?

what key checkpoints occur during each phase of the cell cycle?

Answer 1

• M phase: mitosis
  
  • checkpoint of metaphase:
    
    • are all all chromosomes attached at the spindle before anaphase so that one copy goes in each direction?
• G1: growth phase post mitosis
  
  • environment checkpoint - is it a “favorable environment” to repeat process & make a new daughter cell?
  • DNA damage check point:
    
    • p21 (CKI) modulation of S-cdks
• S: DNA replication
• G2: gap before mitosis
  
  • checkpoint of S-phase:
    
    • all the DNA get replicated?
    • any damaged DNA get repaired?

Question 2

breifly - what are the role of cyclins?

Answer 2

• cyclins are cell cycle proteins that
  
  1. monitor what stage the cycle is in
  2. tell the cycle when to proceed, which they do by.
     
     • binding to cyclin dependent phosphylases (CDKs). CKDs phosphorylate & activate cell cycle proteins, moving the process forward

Question 3

• how do cyclins dictate transitions the steps of the cell cycle?
• what other players are involved?

Answer 3

• during each cell cycle phase, there are certain cyclins that accumulate. (see chart)
  
  • when these cyclins rise to a high enough [] they form cyclin-CDK complexes (example: M-Cdk) with phase-specific CDKs.
    
    • upon formation, the majority of cyclin-CDK complexes are inactive, since CDKs are maintained in a phosphorylated, inactive state by inhibitory kinases (Wee-1)
    • however, a few rouge CDKs won’t be phosphorylated, and will thus form active cycline-CDK complexes with kinase capacity.
      
      • these complexes will phosphorylate & activate Cdc25
        
        • Cdc25 is a phosphotase that will dephosphorylate & activate the inactivive CDK-cyclin complexes.

Question 4

list the cyclins & CDKs that rise in each cycle

Answer 4

Question 5

what is Wee1?

what is its role in the cell cycle?

Answer 5

• an inhibitory kinase
• phosphorylates (most) Cdk such that it stays in an inactivate state

Question 6

• what is Cdc25?
• what is its role in the cell cycle?
• when is it active?

Answer 6

• Cdc25 is a phosphotase - its role is to dephosphorylate & activate inactive cyclin-cdk copmlexes
• though its a phosphotase, it’s active in a phosphorylated state (done by active cyclin-ckd)

Question 7

why is there a rapid increase in M-cdk complexes (M-cyclin + ckd) despite the fact that M-cycline rises steadily before mitotisis?

Answer 7

because most M-cdk complexes will be inactive upon formation. once one active M-cdk complex is formed, it can trigger a positive feedback loop by phosphorylating Cdc25, which can activate all other M-cdk complexes

Question 8

• what are CKIs?
• what is their role in the cell cycle?
• what are the variations of CKIs?

Answer 8

• cyclin dependent kinase inhibitors
• small proteins that bind to an active cyclin-cdk complexes to prevent its function (i.e., its kinase activity)
  
  • they likely inhibit S-Cdks (Cyclin-A + Cdk-2) in order to hold the cell in G1 phase
• CDKIs: p16, p21, p27

Question 9

• what is APC (anaphase promoting complex)?
• what is its role in the cell cycle?

Answer 9

• APC is a ubiquinating protein that triggers the rapid loss of cyclins
  
  • ​it poly-ubiquinates S-cyclins & M-cyclins (?) at the and the end of S-phase, directing them to the proteosome for degredation

Question 10

what points of the cell cycle would be halted by the inhibition of the

• Cdc-25
• APCs
• CKIs

Answer 10

• Cdc-25: dephosphorylates & activates cyclin-CDK complexes (M-CdK)
• APCs: ubiquinates & inactivates cyclins in cyclin-CKD complexes (S cyclin, M cyclin)
• CKIs: binds & inactivates cyclin-CDK complexes (S-Cdk during G1)

Question 11

• what is p21?
• what is its role in cell cycle & how does it do this?
• how is it regulated?

Answer 11

• a CKI (cyclin-dependent kinase inhibitor)
• binds & inhibits cyclin-Cdk complexes:
  
  • specifically, S-Cdk forming at the end of G1, holding the cycle in G1
• is synthesis is induced by DNA damage:
  
  • _​_DNA damage actives protein kinases that phosphorylate & activate p53
  • active p53 binds a regulatory region of the p21 gene,
    
    • inducing p21 transcription

Question 12

cohesin & condensin?

Answer 12

• cohesin: bind to DNA before replication & holds the two sister chromatids together
  
  • ​its regulation is in moving from metaphase to anaphsae in Mitosis and Meiosis II
• condensin: compacts recently replicated DNA loops

Question 13

spindle formation / growth

• spindles are made of what kind of cytoskeletal element?
• when does the formtaion of the spindle start?
• how does the structure of the spindle change throughout different phases of the cell cycle? what are its key components?

Answer 13

spindles are made of microtubules

• In G1: spindle first appears. is a centrosome + extending microtubules
• In G2/S: spindle replicates
• In M:
  
  1. formation of outer, short microtubules - aster microtubules - pull the spindle apart into two centrosomes
  2. longer microtubules - interpolar microtubules - extend into the cell from opposite centromes and overlap w/eachother
     
     • recruit motor proteins to line up at these overlapping regions

Question 14

what is the

• centromere?
• kinetichore?

Answer 14

• centomere: portion of the chromosome at which the kinetchore microtubules attach
• kinetchore: protein complex at the centromere-microtubules attachment site
  
  • centromere + kinechore microtubues + other proteins

Question 15

what is required for metaphase to move into anaphase?

what permits this?

Answer 15

1. perfect metaphase plate alignment
   
   • which means:
     
     • chromsomes in the center
     • kinechore microtubules attached to each side of chromatides
   • depends on:
     
     • microtubule behavior in early metaphase:
       
       • ​interpolar microtubules moving towards eachother to align chromatids
       • any microtubules movin away from eacother becoming degraded
2. anaphase promoting complex

Question 16

anaphase promoting complex ubiquinates what molecules? trigger what processes?

Answer 16

ubiquinates and degrades

• S and M cyclins
  
  • moving cell cycle out of S-phase / M=-phase
• securase
  
  • intiating anaphase
  • in response to proper alignment at metaphase plate

Question 17

discuss the role of APC moving into anaphase

• response to what signal?
• acts on what proteins?
• outline this process

Answer 17

• response to proper alignment at metaphase plate
• steps:
  
  • ubuquinates & degrades securin, which inhibits separase
  • free, active separase can now cleave cohesin
  • chromatids can now separate –> anaphase