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CMCB Fall > Mitosis and Meiosis #16 > Flashcards

Mitosis and Meiosis #16 Flashcards

1
Q

Learning Objectives

A
  1. Describe structural and functional attributes of the mitotic spindle
  2. Explain key evens in various phases of cell division with an emphasis on cytoskeletal dynamics
  3. Describe the mechanisms of anaphase
  4. Compare and contrast key differences between mitosis and meiosis
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2
Q

In somatic cells, cell cycle divided into

A

Interphase (cell growth)

Cell Division

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3
Q

Interphase consists of:

A

G1, S, G2 stages of cell cycle

DNA replication occurs during S phase

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4
Q

What is a mitotic spindle

A

specialized arrangement of microtubules and associated motors that are essential for cell division in somatic cells

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5
Q

What are stages of Mitosis (5)

A

Prophase, prometaphase, Metaphase, Anaphase, Telophase

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6
Q

What happens to MT when mitotic spindle is organized

A

dramatic reorganization of cell’s MT

used to separate the replicated chromosome

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7
Q

What is cytokinesis

A

division of cystoplasmic contents that overlaps somewhat with nuclear division

Begins late anaphase and continues through telophase

Actin-myosin system invovled in cytokinesis

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8
Q

When does mitotic spindle BEGIN to form

A

during early prophase (in cytoplasm)

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9
Q

What is main component of mitotic spindle?

A

Microtubules

Many different MAPS (kinesin-related proteins and dyneins) and other regulatory proteins are present

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10
Q

IS Mitosis dependent on DYNAMIC properties of MTs?

What are antimitotic drugs?

A

YES! The ability to polymerize and depolymerize as wella s their ability to bind motor proteins is important

Drugs (colchicine-destabilizier; taxol-stabilizier) or conditions (cold, calcium) whcih affect MT stability , blocks mitosis

Drugs that either stabilize or destabilize MT structure and affect its funciton –> also affect mitosis

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11
Q

What does Cochicine do to MTs?

A

Depolymerizing agent

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12
Q

What does Taxol do?

A

Stabilizing agent for MTs

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13
Q

What are vinblastine and vincristine?

A

tubulin-sequestering drugs (depolymerize?)

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14
Q

Do these drugs only specify to mitotic spindles of cancer cells?

A

no. they also interfere with mitotic spindles of healthy cells as well as MT in non-dividng cells like neurons

side effects of chemotherapy with these drugs - GI isseus and neuropathy

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15
Q

What happens when there is abnormal spindle fucntion?

A

cells with genetic abnormalities are produced

duaghter cells can have missing or extra chrocomosmes

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16
Q

When does duplication of CENTROSOME occur?

A

Initiates during INTERPHASE as two halves of centriole separate and each serve as templaes for forming another half

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17
Q

What do new centrosome mature as

A

Mature as pericentriolar material enriched in gamma tubulin ring complexes

Centrosomal complex and do not begin to move to opposite poles of cell until prophase is initiated

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18
Q

As they move to opposite pole,s what to replicated centrosomes act as?

A

organizing regions for each half spindle

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19
Q

what happens when centrioles are duplicated?

A

They remain together in a large complex

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20
Q

Are centriole halves identical? How?

A

no!

The “mother” centriole is lager and more complex

Only mother centriole is ass. with pericentriolar matrix that nucleates MTs

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21
Q

Which centriole is assocaited with pericentriolar matrix that nucleates MTs

A

Mother Centriole

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22
Q

Are abnormalities in centrosome number, size, or shape common in many tumor cells?

A

YES

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23
Q

What do Centrosomal Defects result in?

A
  1. Spindle Abnormalities
  2. Chromosome missegregation and aneuploidy
  3. Hallmark of tumors
  4. Because interphase centrosome nucleate and organizes the microtubule cytoskeleton, centrosome abnormalieis could also contribute to disruption in teh overall cellular architercture of tumor cells
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24
Q

What is it beleived that aneuploidy is repsonsible for? (unbalanced completment of chromosomes?)

A

Could produce imbalance between growth-promotoing oncogenes and grwoth-regulating tumor suppressor genes –> lead to cancer

25
Q

What are three types of MTs in fully formed mitotic spindle?

A
  1. Interpolar MT
  2. Kinetochore MT
  3. Astral MT
26
Q

What are Interpolar MT

A

Extend form 2 poles of spindle towards equator

Most numberous f MTs

Overlap with polar fibers from other pole which have opposite polarity (mirror image)

27
Q

What are kinetochore MT?

A

Attached to kinetochore structure of chromatids and extend towards spindle poles

28
Q

What are Astral MT

A

radiate out from spindle poles towards cell membrane

29
Q

Polariities of each half spindle is the same

Where is +/- for each MT type in spindle

A
  1. Plus end (fast growing end) is DISTAL from its spindle pole

Centrosome at spindle pole is ass. wth minus end of MT

Kitetochore and polar MTs, the + end is nearest the equator

Astral MT, + end is closest to cell membrane

30
Q

What is a key step during prophase for spindle formation

Why?

A

Breakdown of nuclear evelope (late prophase, or prometaphase)

many of the motor proteins and MT regulators that promote spindle assebmly and function are in the nucleus

31
Q

What is invovled in chromosome condensing during prophase?

A

Protein kinase

32
Q

what triggers nuclear membrane breakdown in late prophase (prometapahse)

A

phosphorylation of elements in teh nuclear pore complex and nuclear lamina

kinetochore MT begin to form, stiumualte dby local environemnt of chromcosomes, and begin to capture chromatids

33
Q

Dramatic changes in MT stability during early mitosis how?

A

1/2 life of avg MT decrease by 20x as cell enters prophase and may cytoplasmic MT disappear

This provides tubulin subunits to build spindle apparatus and enable rapid MT turnover

34
Q

hat proteins are invovled with destabilizing MT arasys?

A

Catastrophic factors increase catastrophes

MAPS are invovled with increasing frequency of rescues

35
Q

How does spindle self organize by MT motors

A

Nucleation

Antiparallel cross linking by kinesin

Outward push by kinesin

Focus of poles by dynein and kinesin

pushing, pulling, slididng, tugging until poles are properly positiioned

36
Q

What is cytosolic dynein involved in?

expt?

A

Formation and stabilization of mitotic spindle poles

Cytosolic dynein-minus end directed motors is involved in consolidating normal FOOTBALL LIKE shape of spindle

Expt: blocked bytosolic dynein –> abbrantly formed spindle

37
Q

where are kintetochore MT attached?

A

Centromere that bind sister chromatids together

38
Q

Where are kinetochore + ends?

A

proximity to kinetochore!

39
Q

What DNA controls genetration of a kinetochore?

A

CEN DNA (centromeric DNA) which rectruites and binds various proteins that make inner layer of kinetochore

40
Q

What way of growth of kinetochore MT?

A

while plus end appears to be capped in kinetocohore, remains active MT end that undergoes assebmly/disassembly reactions

41
Q

How are chromosmes “captured” by MT?

A

Highly dynamic MT in late prophase probe , search, and capture

gorwign and shrinking + ends –> allows some MTs to grap or capture a kinetochore

MOre often, kinetocore encounters MT side wall rather than teh end–> motor proteins slide kinetochore to + end of MT –> captures MT

When both kiethcores properly attached, fibers are stabilitzed

42
Q

Describe balance of forces in metaphase spindle

A

Opposing forces (pusha nd pull) align chromosome on equatorial plate as cell approaches metaphase

43
Q

What is polar ejection force?

A

acts on chromosome arm that is severed from its kinetochore and quicly moves away form pole (push) while other half with kinetochore is pulled

44
Q

What is a spindle assembly checkpoint?

A

only after ALLLL kinetochores are captured and chromosomes are aligned on equator will cell intitate anaphase

45
Q

When does dell intiate anaphase?

A

only AFTER ALL kinetochore captured

46
Q

What happens during anaphase gnerally?

A

shortest part

chromosomes seaprate and move to poles

47
Q

What happens at telophase general

A

reformation of nuclear enveoleme

decondensation of chrocosomes

48
Q

Chromatid separation triggers anapahase

Anaphase entry-the separation of chromatid

A

very start of anaphase, sister chromatidds break apart

cohesin complexes taht connect chromatids along lenght are cleaved after degradation of an inhibitor to a protease which targets cohesin occurs

ca

49
Q

What are the two stages of Anaphase?

A

Anapahse A (early)

Anaphase B (alte)

show differential sensitivity to various drugs and inhibitors–suggesting that different mechanisms are involved in each phase

50
Q

What happens during anaphase A?

A

during which chromatids move towards teh pole and kinetochore MT shorten

movement of daughter chromosomes to poles

forces generated mainly at kinetochore

51
Q

What happens during anaphase B?

A

spindle elongates and poles of spindle move further apart

  1. sliding force is generated b/w interpolar microtubules from opposite poles to push poles apart

INterpolar MT elongate

  1. pulling F acts directly on poles to move them apart
52
Q

Mechanisms of anaphase A involve active MT disassembly

A

Evidence suggests that motor proteins are NOT directly involved since this step has been documeted in teh absence of ATP

53
Q

Anaphase B requires 3 processess: What are they?

A
  1. Pushing Force
  2. Pulling force (all of which require energy and
  3. net assebmely which increases MT length
54
Q

Does Anaphase B require ATP?

A

yes, requires motor proteins at pole

55
Q

What else happens during Anaphase B?

A

regions of microtuble overlap at midzone becomes shorter –> antibparallel polar MTs from oppsote poles slide relative to each otehr

Interpolar MTs get loner,

Cytosolic dynein, minus-end directed motor protein involved in moving poles further apart

56
Q

Kinesin-relsted proteins

A

KRPS appear to be involved

57
Q

Describe what occurs during cytokinesis

A

Nuclear and Cytoplasmic (cytokinesis) are separate events

In vertebrates, mitotic spindle poles (centrosomes) play essential role in determining positionging and timing of cytokinesis

58
Q

When does cytokinesis begin?

A

anaphase and contineus through telophase and into interphase

59
Q

What kind of cytoskeleton does cytokinesis use?

A

Actin/myosin II interactions

CMCB Fall (17 decks)

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