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BMSC 220 > Chapter 13 > Flashcards

Chapter 13 Flashcards

1
Q

What is the cell cycle?

What are the 4 coordinated processes in eukaryotic cells?

A

Cycle of growth and division within a cell
4 processes:
1. Cell growth
2. DNA replication
3. Distribution of the duplicated chromosomes to daughter cells
4. Cell division

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2
Q

What are the 2 general phases of the cell cycle?

A
  1. Mitosis (M phase)- involves nuclear division (karyokinesis)
    Results in cytokinesis (division of cell following mitosis)
    Contains distribution of duplicated chromosomes to daughter cells (3) and cell division (4)
  2. Interphase- period between mitosis when the chromosomes are decondensed and distributed throughout the nucleus (makes nucleus morphological uniform)
    Contains cell growth (1) and DNA replication (2)
    Slide 12
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3
Q

How do embryos divide at a different rate than other cells?

A

Only have M and S stages so it is extremely rapid

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4
Q

How can cell division be reactivated?

What is the non dividing stage called?

A

Can be reactivated by appropriate extracellular signals such as growth factors (ex: skin fibroblasts)
Neurons and many other cell types remain in a quiescent, non dividing phase known as G0 stage (cells remain metabolically active but do not proliferate)

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5
Q

How is the progression of cells through the division cycle regulated?
What are the two questions a cell faces prior to initiating the processes leading to mitosis and cell division?

A

Progression of cells through division cycle is regulated by extracellular signals from environment or internal signals that monitor and coordinate processes in cycle phases
Two questions cell faces:
1. Should I divide?
2. Am I capable of dividing properly?

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6
Q

What is the decision point?

A

Decision point in late G1 phase is called “START” in yeast cells, or the restriction site in animal cells

Once a cell passed the decision point, it is committed to proceed through S phase and the rest of the cell cycle

Slide 20 and 21

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7
Q

What are the 4 cell cycle checkpoints?

A

These control the “am I capable of dividing properly” question
G1- ensures damaged DNA is repaired before being relocated in S phase
S- continues monitoring DNA integrity ensures DNA that is damaged during replication is repaired
G2- prevents initiation of mitosis if DNA is not completely replicated or is damaged
G1, S, and G2 are DNA damage checkpoints
M- spindle assembly checkpoint, inhibits spindle assembly if chromosomes not distributed accurately to daughter cells
Slide 23

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8
Q

What are the two groups of highly conserved proteins that control the cell cycle (C and C)?

A

Cyclins- proteins which regulate the activity of the enzymes which regulate the cell cycle
Cyclin dependant protein kinases (Cdk’s)- phosphorylating enzymes that are regulated by cyclins

Interaction of cyclins and Cdk’s are responsible for triggering major cell cycle transitions and progress cell cycle through it’s major checkpoints

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9
Q

What are the 3 initial distinct experimental approaches to identification of key molecules (cyclins and Cdks) responsible for cell cycle regulation? (Frog oocytes, yeast, and sea urchins)

A

Frog oocytes- key factor in cytoplasm slides 30-31
Yeast- protein kinase slides 32-33
Sea urchins- cyclic protein expression slides 34-35

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10
Q

What is the maturation promoting factor (MPF)?

Whats it’s structure?

A

Frog oocyte maturation triggers entry into meiotic division from G2 arrested oocytes which is identified MPF
It is composed of two key subunits:
Cdk1 and cyclin B
Slide 36-37

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11
Q

Who discovered the START site in yeast and concept of cell checkpoints?
Who discovered cyclins?
Who discovered CDK?

A

Leland H Hartwell- START and concept of cel checkpoints
R. Timothy (Tim) Hunt- cyclins
Paul M. nurse- CDK

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12
Q

What must CDK1 do befire it can phosphorylate other proteins to initiate entry to M phase?

A

It must first undergo a number of phosphorylation and depshosphorylation events itself
After CDK1 binds to cyclin B in G2, it is phosphorylated in 3 positions, then dephosphorylated 2 of these positions to become active MPF and allow cell into M phase
Slide 41

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13
Q

What are the 5 stages of how CDK1 is regulated?

A
  1. CDK1 alone unphosphorlyated
  2. Cyclin B binds to CDK1 (in G2) = MPF
  3. CDK1 is phosphorylated at 3 sites: 1 activating site, 2 inactivating sites (the 2 inactivating sites mask the activating site)
  4. The 2 inactivating sites are dephosphorylated allowing the singly phosphorylated CDK1/Cyclin B complex to activate other proteins that carry cell into mitosis
  5. Activated CDK1 = degradation of Cyclin B
    Slide 42-43
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14
Q

What are CDK’s dependant on?

A

CDKs are cyclin dependant protein kinases that control the cell cycle of eukaryotes
Slide 45

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15
Q

What happens during mitosis (Karyokinesis) and cell division (cytokinesis)?
What role does the CDK1/cyclin B complex play?

A

Mitosis- chromosomes condense, nuclear envelope breaks down, cytoskeleton reorganizes to form mitotic spindles, chromosomes move to opposite sides
Cell division- Golgi apparatus fragments and cytoplasm divides

CDK1/Cyclin B complex ultimately regulates all of these aspects of karyokinesis and cytokinesis

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16
Q

What are the 4 key processes of CDK1/cyclin B complex during mitosis?

A
  1. Chromatin condensation- phosphorylation of condensins
  2. Nuclear envelope breakdown- phosphorylation of lamins, nuclear pore complexes
  3. Fragmentation of Golgi apparatus- phosphorylation of Golgi matrix proteins
  4. Spindle formation- phosphorylation of centrosome and microtubule proteins
17
Q

What are cohesins and condensins?

A

Cohensins- proteins that bind to DNA in S phase & maintain the linkage between sister chromatids following DNA replication
Condensins- activated by phosphorylated CDK1 and replace the cohesins

Slide 51

18
Q

How are the chromatids separated after degradation of cyclin?

A

APC/C is originally inactivated then gets activated in anaphase which results in degradation of cyclin B and degradation of remaining cohesion proteins allowing separation of chromatids
Slide 52

19
Q

How is the nuclear envelope broken down?

A

Driven in part by phosphorylation of of nuclear lamins by CDK1/Cyclin B which causes lamins to depolymerize
Slide 53

20
Q

How is cytokinesis triggered?

A

Inactivation of CDK1

Contractile ring of actin and myosin filaments forms beneath plasma membrane beginning in anaphase

21
Q

What are D type cyclins?

A

The link between growth factor signalling and cell cycle progression in animal cells
Cyclin D synthesis drives cells past restriction point and allows for continued cell division
Slide 57

22
Q

What is the tumor suppression Rb?

A

Key substrate of CDK4/Cyclin D
Tumor suppression gene is a gene whose inactivation leads to tumor development
Rb is transcriptional regulatory protein that controls cell cycle progression

Tumor suppression genes act like brakes for cell proliferation

23
Q

What leads to the progression of cell cycle past the restriction point in G1 and move into S phase?

A

Presence of growth factors stimulate Cyclin D expression which phosphorylates Rb which allows E2F to activate genes required for progression of cell cycle past the restriction point
Slide 59

24
Q

How is cell cycle arrest initiated at DNA damage checkpoints?

A

Initiated by protein kinases (called ATR and ATM) which are components of protein complexes that recognize damaged and unreplicated DNA
These kinases phosphorylation and activate checkpoint kinases (Chk1 and Chk2)

25
Q

What is p53?

A

Transcription factor that is stabilized and activated by phosphorylation from ATM and Chk1
Results in large intracellular increase in p53 levels which induces the expression of a Cdk inhibitor which results in cell cycle arrest which allows for repair of damaged DNA
P53 is a TUMOR SUPRESSOR
Slide 62

26
Q

What are oncogenes?

A

Proteins such as cyclin D and Ras induce cell proliferation and are referred to as oncogenes
Mutations causing unregulated synthesis of Ras or Cyclin D stimulate proliferation which remains unchecked

27
Q

What is apoptosis?

A

Cells are normally lost in tissues due to sloughing off, necrosis, or an active process known as apoptosis
Programmed cell death which is carefully regulated so that the date of individual cells meets the needs of the organism as a whole
Removed damaged or non functional or unwanted cells from tissue
Abnormalities in apoptosis are associated with diseases like cancer
Characterized by cleavage of chromosomal DNA
Slide 68

28
Q

Why is using C elegans good for apoptosis study?

A

Short life cycle (good genetic model)
Transparent- cells easily viewed in development
Has a determinate cell lineage

29
Q

What is caspase?

A

Proteases thatbare the executioners of apoptosis and initiate many of the degradative processes of apoptosis
Exist in the cell as inactive precursors and are activated by proteolytic cleavage

BMSC 220 (12 decks)

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