White Lecture 4 "Cell cycle 2" Flashcards

1
Q

Describe condensin

A

five subunit protein complex

related to cohesin; protein that holds sister chromatids together

2 SMC subunits and 3 Non-SMC subunits

forms a ring like structure and uses ATP to promote compaction and resolution of sister chromatids

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2
Q

What is the 2 step process that avoids the chromatids being broken when they are being pulled apart

A
  1. chromosome condensation and resolution
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3
Q

Define resolution

A

sister chromatids become distinct separate units

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4
Q

Describe the mitotic spindle

A

bipolar array of microtubule proteins

pulls sister chromatids apart at anaphase

M-CDK triggers the assembly

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5
Q

Describe tubulin

A

heterodimer of alpha and beta tubulin with non-covalent bonds

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6
Q

What is the plus end of the microtubule?

A

The fast growing end

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7
Q

What is the minus end of the microtubule?

A

The slow growing end

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8
Q

What are the 3 types of microtubules?

A
  1. kinetochore
  2. interpolar microtubules
  3. astral microtubules
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9
Q

Define kinetochore microtubules

A

attach each chromosome to the spindle pole

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10
Q

Define the inter polar microtubules

A

Hold two halves of the spindle together

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11
Q

Define astral microtubules

A

Interact with the cell cortex

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12
Q

What does the plus end of the kinetochore tubules attach to?

A

attach to the sister chromatid pairs at large protein structures called kinetochores and to the centrosome

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13
Q

What does the plus end of the inter polar microtubules attach to?

A

The plus end of one pole interacts with the plus end of the other

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14
Q

Describe the astral microtubules in the cell

A

radiate outward from the poles and contact the cell cortex helping to position the spindle in the cell

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15
Q

Define the MTOC

A

Where all the microtubules are nucleated from;

microtubules grow outward from the MTOC from the plus end

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16
Q

What is the gamma tubulin ring complex

A

responsible for the nucleation of the microtubule growth

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17
Q

What is the function of gamma turc

A

binds to the negative end and elongates the microtubules

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18
Q

Describe centrioles

A

protein organelles called a centrosome

consists of a matrix and a pair of centrioles

contains gamma turc

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19
Q

What are the two types of motor proteins?

A

Dyneins and kinesins

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20
Q

Describe dyneins

A

tends to move toward the center of the cell

minus end is directed to the microtubule motor

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21
Q

Describe kinesisns

A

tend to move toward the periphery
walks toward the positive end of microtubules
has 2 globular heads and elongated coil coil tails
plays an important role in chromosome separation

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22
Q

What is dependent on the motor proteins?

A

assembly and function of the mitotic spindle

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23
Q

What are the 4 major proteins that are involved in the spindle assembly and function?

A
  1. kinesin-5
  2. kinesin- 14
  3. kinesin- 4, 10
  4. dynein
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24
Q

Describe kinesin-5

A
  • made up of two motor proteins that interact with the plus end of the anti-parallel microtubule
  • move two anti-parallel microtubules past each other to force the spindle poles apart
  • moves towards the plus end and forces the chromosomes apart
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25
Q

Describe Kinesin-14

A
  • minus oriented directed motor with a single motor domain

- move toward the minus end and pulls the poles together

26
Q

What happens if there is not kinesis-5 present in the cell

A

the spindle collapses

27
Q

Describe kinesin-4,10

A

also called chromokinesins

move toward the plus end

push attached chromosomes away from the pole

28
Q

How are the chromosomes brought back to the centrosome?

A

via the push pull motion’ the kinesin 4, 10 pushes toward the plus end of the inter polar or astral microtubule and the kinetochore microtubules pulls it back

29
Q

Describe dyneins

A

minus end directed motors
links the plus ends of the astral microtubules to the actin skeleton at the cell cortex
moves toward the minus end of the microtubule, the dynein motors pull the spindle poles away from each other

30
Q

Describe kinetochores

A

giant multi-layered protein structure that is built on the chromosome

allows for attachment of the spindle to the chromosomes

has multiple microtubules attached to it

31
Q

Describe the exposed end of the kinetochore

A

there is an exposed open end that allows for the addition and removal of tubulin subunits

32
Q

Describe the binding of the kinetochore

A
  • bipolar attachment
  • attach the kinetochore to the microtubule on the opposite side of the chromosome
  • sister chromosomes attach to opposite poles of the spindle
33
Q

How is stable attachment detected by the kinetochore?

A

Tension

34
Q

What are the 3 forces that are involved in chromosome movement

A
  1. depolymerization
  2. microtubule flux
  3. polar ejection force
35
Q

describe depolymerization

A

major force pulls the kinetochore and the chromosome toward the spindle

depolymerization of the plus end of the microtubule pulls the kinetochore poleward

36
Q

Describe microtubule flux

A

microtubules move towards the spindle pores while being dismantled at the minus ends

tubulin is added at the plus end while being removed at the minus

ESCALATOR

37
Q

Describe the polar ejection force

A

kinesin-4, 1o motors on the chromosomes interact with microtubules and transport chromosomes from the poles

push pull phenomenon

38
Q

What are the final steps of mitosis?

A
spindle is prepared 
organization 
sister chromatids separate 
m-cdk activates APC/C 
cohesin system
39
Q

Describe anaphase A

A

chromosomes move apart due to the depolymerization at the kinetochore

40
Q

Describe anaphase B

A

The separation of spindle poles themselves by kinesin-5 motor proteins

41
Q

Describe cytokinesis

A

final step of the cell cycle

at the end of anaphase

42
Q

What are the 4 stages of cytokinesis?

A
  1. initiation
  2. contraction
  3. membrane insertion
  4. completion
43
Q

Describe the contractile ring

A

causes the cleavage furrow and is made up of actin and myosin

formin helps in the formation of the ring as it is making the actin

44
Q

What are the class 1 extracellular signaling molecules?

A

mitogens- stimulate cell division by triggering G1/S-cdk activity

45
Q

Describe the Class 2 extracellular signaling molecules

A

growth factors

46
Q

Describe the class 3 extracellular signaling molecules

A

survival factors suppress form of programmed cell death known as apoptosis

47
Q

What happens if just one of the classes of the extracellular signaling molecules that is involved in controlling cell division is missing?

A

CANCER

48
Q

Describe mitogens

A

act when more cells are needed

49
Q

Describe the action of the mitogens

A
  1. mitogen binds to the receptor
  2. Ras causes activation of the MAP kinase cascade
  3. leads to the increase of gene regulatory proteins including Myc
  4. Myc promotes entry into cell cycle by increasing the expression of G1 cyclins and get active G1 Cdk-Cyclin
50
Q

What does the G1-Cdk-cyclin activate and describe what happens after that

A

E2F proteins are activated

binds to the promotes of the G1/S cyclin and the S cyclin genes –> transcription

enter the S phase of the cell cycle

DNA synthesis begin

51
Q

What is the function of the Rb protein? And what does this action cause?

A

Inhibits E2F which shuts down the entry into the S phase of the cell cycle

Rb is a tumor supressor

52
Q

What happens if the Rb protein is not working?

A

There is not control and therefore CANCER can occur

53
Q

Describe retinoblastoma protein family

A

Loss of copies of the Rb genes which leads to cell and tumor proliferation of the retina;

54
Q

Which protein kinases are activated if there is DNA damage?

A

ATM and ATR protein kinases

55
Q

What do the ATM and ATR genes do when the damaged DNA is detected?

A

phosphorylate Chk1 and Chk2 proteins

56
Q

What is the major target of the Chk1 and Chk2 proteins?

A

p53 protein which stimulates the p21

57
Q

Describe ataxia telangiectasia

A

ATM protein is defective; autosomal recessive; no DNA repair

58
Q

In what percentage of cancers is Ras mutated?

A

30%

59
Q

In what percentage of cancers is p53 mutated in?

A

50%

60
Q

Describe the PI-3 kinase pathway

A

adds ATP to inositol phospholipids

activates TOR which activates factors for cell growth

61
Q

What are the three mechanisms that coordinate cell growth?

A
  1. Rate of cell division is determined by extracellular factor
  2. cell growth and division is controlled by growth factors and mitogens
  3. cell growth and division both stimulated by extracellular factor
62
Q

What does myostatin do?

A

inhibits cell growth