White Lecture 3: "Cell Cycle 1" Flashcards

1
Q

What are the 3 basic steps in the cell cycle?

A
  1. Cell growth and chromosome replication
  2. Chromosome segregation
  3. Cell division
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2
Q

What is the goal of the cell cycle?

A

To produce two genetically identical daughter cells

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3
Q

What is the main challenge of the cell cycle?

A

Mistakes!

About 6 are made per 1 cell division

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4
Q

What is an example of a cell that needs to be constantly replaced by the cell cycle?

A

Intestinal cells and erythrocytes

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5
Q

How many cells are in the body? And how many cell divisions occur in one lifetime?

A

3.0 * 10^13 cells in the body and

10^16 cell divisions

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6
Q

Describe the RBC’s that are in the body; how many are there? How long do they last? How many do you make a second?

A

A college student has 25 trillion

last 120 days

are removed from circulation and need to be replaced

2.4 million RBC’s produced per second…WUT.

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7
Q

Define cancer

A

Disease of excess cell proliferation

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8
Q

What is the cell-cycle control system?

A

ordered series of biochemical switches that responds to signals inside and outside of the cell

can regulate the cell number as well

proteins coordinate events in the cell cycle so that they occur at the right time

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9
Q

What happens if the cell-cycle control system malfunctions?

A

Cancer can result

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10
Q

What are the 3 major chromosomal events in the cell cycle?

A
  1. chromosomal duplication
  2. chromosomal segregation (mitosis)
  3. cytokinesis
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11
Q

What are the 4 phases of eukaryotic cell division?

A
  1. prophase
  2. metaphase
  3. anaphase
  4. telophase
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12
Q

Describe prophase

A

chromosomes condense into sister chromatids

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13
Q

Describe metaphase

A

sister chromatids line up at the equator of the cell

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14
Q

Describe anaphase

A

sister chromatids become daughter chromosomes and are pulled to the opposite poles of the spindle

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15
Q

Describe telophase

A

spindle disassembles, chromosomes are packaged separately, cytokinesis

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16
Q

What are the 4 phases of the cell cycle?

A

g1
S
G2
M

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17
Q

Describe the GAP phases of the cell cycle

A

cells have extra gap phases to allow more time for growth

G1 phase between M and S and G2 between S and M

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18
Q

What are the 3 phases that occur during interphase?

A

G1 S G2

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19
Q

What are the 3 major transition checkpoints of the cell cycle?

A

G1 to S

G2 to M

anaphase and cytokinesis in the M phase

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20
Q

Describe Checkpoint 1

A

START- cell commits to the cell cycle entry and chromosome duplication (restriction point)

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21
Q

Describe Checkpoint 2

A

G2/M chromosome alignment on the spindle in metaphase

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22
Q

Describe Checkpoint 3

A

metaphase to anaphase transition; trigger sister chromatid separation and cytokinesis

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23
Q

what was used as the model organism to study the cell cycle?

A

Yeast

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24
Q

Describe fission yeast

A

grows by elongation at ends; division occurs when septum or cell plate form midway

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25
Q

Describe budding yeast

A

oval yeast that divides by forming the bud; the bud appears at G1 and grows until mitosis phase

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26
Q

What allowed the discovery of the Cdc genes?

A

Mutant yeast

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27
Q

What happens to the cell cycle if the cells are placed in poor nutrients before the start?

A

The cell cycle entry is delayed and the medium will grow slowly

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28
Q

What happens to the cell cycle if the cells are placed in a poor medium after the start of the cell cycle?

A

The cells will continue into the cell cycle

29
Q

When do cell lines typically cease to divide?

A

after 25-40 divisions

30
Q

Define immortalized cell lines

A

cells grow forever

31
Q

What are immortal cell lines useful in studying?

A

erythroid cell development; and the generation of red blood cells

32
Q

What is the purpose of cdks in the cell cycle?

A

are able to turn on various steps of the cell cycle

phosphorylate proteins downstream to activate them and regulate cell cycle events

33
Q

Describe cdks

A

Heart of the cell cycle control system

activities of the cdks rise and fall

cyclical changes in phosphorylation of substrates downstream that regulate cell cycle events

GOVERN the cel cycle

34
Q

What are the protein that regulate proteins?

A

Cyclins

levels vary in the cell cycle

cdks are dependent on cyclins- must be bound to cyclin to have protein kinase activity

35
Q

True or false: The levels of cdk vary

A

FALSE: they remain constant but their activities may change

36
Q

What is the function of cyclins?

A

controls what step the cell is in in the cycle

direct cdks to their target

37
Q

What are the 4 classes of cyclins?

A
  1. G1/S start cell cycle
  2. S cyclins
  3. M-cyclins- mitosis
  4. G1 cyclins
38
Q

Describe the G1/S start cell cycle cyclins

A

-activates cdks in late g1, triggers progression through the START, commitment to cell cycle entry
levels drop in S phase

39
Q

Describe the S cyclins

A

duplicate DNA

Binds to the cdks after the progression through the start

stimulate chromosome duplication

S cyclin levels are high until mitosis

40
Q

Describe M cyclins

A

mitosis

activate cdks that stimulate entry into mitosis at the g2/m checkpoint

m cyclins are removed at mid mitosis

41
Q

Describe the binding of cyclin to a cdk.

A

prior to binding, the active site of the cdk is blocked by a region of the T loop

binding of the cyclin causes the t loop to move out of the active site

phosphorylation of cdk at the t loop fully activates the enzyme

phosphorylation of cdk caused by CAK

42
Q

Describe what Wee1 Kinase does

A

inhibits the cdk activity by phosphorylating the roof “site”

43
Q

What does cdc25 do?

A

phosphatase that dephosphorylates “roof” site to increase cdk activity

44
Q

Define a CKI proteins

A

Cdk Inhibitory proteins

CKI binds to cdk and cyclin to inactivate

primarily used for control of G1/S-cdks + S-cdks early in cell cycle

45
Q

Describe what INK4A is.

A

INK4A is an inhibitor of cdk that is involved in the G1 phase of the cell cycle

46
Q

What happens if there is a mutation in the INK4A gene?

A

melanoma

cannot control the cell cycle

47
Q

Describe P53 and its relation to P21

A

p53 is a major tumor suppressor that influences the expression of many genes

p21 is one of the genes that p53 up regulates. P21 is a CKI that is supposed to stop cell division

IF p53 fails, then there will be lower p21 expression, then the cells will divide uncontrollably

48
Q

What is the importance of the S-cyclin-cdk complexes?

A

start DNA replication; complexes are generated and inhibited by binding to CKI

released via proteolysis

49
Q

What does proteolysis of CKI’s do?

A

Can turn on S-CDK’s

50
Q

How do you add ubiquitin to CKI’s?

A

SCF-ubiquitin ligase

51
Q

What does the SCF activity depend on?

A

The F-box subunit which helps the SCF recognize the target proteins

adds CKI proteins in G1 and activates S-cdks which restores the activity of the S-cdk complex

52
Q

What controls mitosis?

A

M-cdk

53
Q

What does Wee1 do to M-cdk?

A

holds it in the inactive state so that by the end of g2, there is a lot of inactive M-cdk

54
Q

How is M-cdk activated?

A

by cdc25 protein phosphatase, which removes the inhibitory phosphates from the mcdk

55
Q

Describe the double circuit positive feedback

A
  1. The active Mcdk complex will activate cdc25 phosphatase to remove the phosphate from the roof site- release inhibition
  2. Wee1 kinase is inhibited so that the roof site is not phosphorylated

THIS ACTIVATES MCDK FAST

56
Q

What is the progression from metaphase to anaphase triggered by in mitosis?

A

By protein DESTRUCTION not phosphorylation

57
Q

What is the role of the APC/C

A

anaphase promoting complex- ubiquitin ligase family of enzymes

catalyzes the addition of ubiquitin to the proteins to cause destruction

58
Q

What are the 2 major proteins that are affected by APC/C?

A

cohesin and securin

59
Q

Define cohesin

A

glues the sister chromatids together

SMC proteins (structural and maintenances of chromosomes

rings around the sister chromatids

60
Q

Define securin

A

protects the cohesins by inhibiting separase

61
Q

Describe APC/C in mitosis

A

APC/C levels rise mid mitosis and adds ubiquitin on the targets to destroy proteins

also destroys securin which is the inhibitor of separase

separase is able to cleave cohesin and the chromatids can come apart

62
Q

Which cyclins are the major target of the APC/C?

A

S cyclins and M cyclins

63
Q

Describe the general overview of the cell cycle control system

A
  1. signals cause activation of G1 cdk
  2. g1 cdk stimulates the gene making G1/S cyclin + s cyclin
    Go through START
  3. G1S cdk activity induces Scdk activity causing DNA replication
  4. Mcdk drives the expression through the G2 M checkpoint
  5. APC/C+ cdc20 triggers the destruction of securing and cyclins at the metaphase to anaphase transition and anaphase can occur
64
Q

What are the 4 ways in which the cyclin cdk activities can be regulated?

A
  1. Phosphorylation of the cyclin cdk complex
  2. binding of a CKI
  3. proteolysis of cyclins
  4. ubiquination of proteins
65
Q

What are the two parts of regulation in mitosis?

A
  1. increase in the Mcdk activity at the G2/M—- prophase and metaphase can occur
  2. metaphase to anaphase transition
66
Q

What are the two problems that a cell must solve in DNA replication?

A
  1. conduct replication accurately to avoid mutations

2. only copy each nucleotide ONCE

67
Q

What are the 2 steps of DNA replication?

A
  1. G1 phase the prereplicative complex assembles at the origins of replication
  2. at the S phase, the replication forks are created
68
Q

True or False During mitosis no new PRE replicative complexes are made

A

TRUE

69
Q

What inhibits the PRE-RC activity

A

CDK

WHILE Scdk and Mcdk are high during the S and M stages, no PRE-RC is formed